rs853600

Variant names:

• chr10-118139636-C-A
• rs853600
• ENST00000435944.5:n.453-66886C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000435944.5(CASC2):​n.453-66886C>A variant causes a intron 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 ENST00000435944.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CASC2	NR_026939.1	n.456-66886C>A		intron_variant	Intron 3 of 4
CASC2	NR_026940.1	n.456-67800C>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC2	ENST00000435944.5	n.453-66886C>A		intron_variant	Intron 3 of 4	1
CASC2	ENST00000414722.5	n.542-66886C>A		intron_variant	Intron 3 of 3	5
CASC2	ENST00000439517.2	n.155-66886C>A		intron_variant	Intron 2 of 3	5

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

African (AFR) AF: 0.204 AC: 8450 AN: 41454

American (AMR) AF: 0.413 AC: 6290 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1792 AN: 3470

East Asian (EAS) AF: 0.148 AC: 763 AN: 5150

South Asian (SAS) AF: 0.581 AC: 2796 AN: 4810

European-Finnish (FIN) AF: 0.634 AC: 6669 AN: 10522

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40361 AN: 67928

Other (OTH) AF: 0.477 AC: 1005 AN: 2106

Alfa AF: 0.568 Hom.: 12744

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
PhyloP100		-2.4

Splicing

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

Other links and lift over

dbSNP: rs853600; hg19: chr10-119899147;