A germline mutation of CDKN2A and a novel RPLP1-C19MC fusion detected in a rare melanotic neuroectodermal tumor of infancy: a case report

Table 1 Germline variants in the MNTI

Gene	Variant type	Chr	Position	Ref/Seq	Amino acid	Transcript	Read depth	Existing annotation (Allelic frequency)	Sift	Polyphen	Condel
CDKN2A	SNV	9	21970916	C/T	Ala/Thr	ENST00000304494.9	322	CM004869 (0.027)	deleterious	benign	neutral
CDKN2A	SNV	9	21971137	T/G	Asp/Ala	ENST00000304494.9	105	COSM4163712 (NA)	deleterious	probably_damaging	deleterious
CHD1	Indel	5	98192165	AGG/–	Pro/Unknown	ENST00000284049.7	NA	NA	NA	NA	NA

No tumor-specific non-synonymous mutations were identified and these variants were also detected in germline DNA extracted from the patient’s blood. A heterozygous T/G mutation on chr 9:21971137 generates a mutant allele of CDKN2A which encodes a p16^INK4A protein with substitution of aspartic acid for alanine at position 74. This change is predicted to be damaging or deleterious by the Sift, Polyphen and Condel algorithms and mutations of Asp74 in CDKN2A are documented in COSMIC as rare tumor variants. The other CDKNA mutation (Ala/Thr) is not predicted to be damaging to the function of p16^INK4A. Common polymorphisms with a dbSNP annotation have been excluded
SNV single nucleotide variant, NA = not available

ISSN: 1471-2407