10-118139636-C-A

Position:

• chr10-118139636-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_026939.1(CASC2):​n.456-66886C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,882 control chromosomes in the GnomAD database, including 18,153 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (18153 hom., cov: 31)
• Consequence: CASC2 NR_026939.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

Genes affected

CASC2 (HGNC:22933): (cancer susceptibility 2) Involved in defense response to tumor cell; negative regulation of MAPK cascade; and positive regulation of cysteine-type endopeptidase activity involved in apoptotic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC2	NR_026939.1	n.456-66886C>A		intron_variant, non_coding_transcript_variant
CASC2	NR_026940.1	n.456-67800C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC2	ENST00000435944.5	n.453-66886C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68697 AN: 151764 Hom.: 18149 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.476

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.452 AC: 68715 AN: 151882 Hom.: 18153 Cov.: 31 AF XY: 0.452 AC XY: 33541 AN XY: 74210

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.477

Alfa AF: 0.567 Hom.: 11434

Bravo AF: 0.420

Asia WGS AF: 0.380 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.016
DANN	Benign	0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs853600; hg19: chr10-119899147;