ENST00000435944.5:n.452+61033G>A

Variant names:

• chr10-118113229-G-A
• rs853637
• ENST00000435944.5:n.452+61033G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000435944.5(CASC2):​n.452+61033G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00729 in 152,166 control chromosomes in the GnomAD database, including 16 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 0.0073 (16 hom., cov: 32)
• Consequence: CASC2 ENST00000435944.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679
• Publications: 1 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=-0.91).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00729 (1109/152166) while in subpopulation AFR AF = 0.0254 (1056/41508). AF 95% confidence interval is 0.0242. There are 16 homozygotes in GnomAd4. There are 509 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435944.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC2	NR_026939.1		n.455+61033G>A		intron	N/A
	CASC2	NR_026940.1		n.455+61033G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC2	ENST00000435944.5	TSL:1	n.452+61033G>A		intron	N/A
	CASC2	ENST00000414722.5	TSL:5	n.541+61033G>A		intron	N/A
	CASC2	ENST00000439517.2	TSL:5	n.154+63612G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00721 AC: 1097 AN: 152048 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00478

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

GnomAD4 genome AF: 0.00729 AC: 1109 AN: 152166 Hom.: 16 Cov.: 32 AF XY: 0.00684 AC XY: 509 AN XY: 74406

African (AFR) AF: 0.0254 AC: 1056 AN: 41508

American (AMR) AF: 0.00236 AC: 36 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67998

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00555 Hom.: 2

Bravo AF: 0.00842

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.56
PhyloP100		0.68

Splicing

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

Other links and lift over

dbSNP: rs853637; hg19: chr10-119872740;