2-47369450-GCCCTCCCGCGAGTCCCGGGC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002354.3(EPCAM):c.-45_-26del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00964 in 1,369,268 control chromosomes in the GnomAD database, including 722 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (406 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (316 hom.)
• Consequence: EPCAM NM_002354.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

Genes affected

EPCAM (HGNC:11529): (epithelial cell adhesion molecule) This gene encodes a carcinoma-associated antigen and is a member of a family that includes at least two type I membrane proteins. This antigen is expressed on most normal epithelial cells and gastrointestinal carcinomas and functions as a homotypic calcium-independent cell adhesion molecule. The antigen is being used as a target for immunotherapy treatment of human carcinomas. Mutations in this gene result in congenital tufting enteropathy. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-47369450-GCCCTCCCGCGAGTCCCGGGC-G is Benign according to our data. Variant chr2-47369450-GCCCTCCCGCGAGTCCCGGGC-G is described in ClinVar as [Benign]. Clinvar id is 1241098.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPCAM	NM_002354.3	c.-45_-26del		5_prime_UTR_variant	1/9	ENST00000263735.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPCAM	ENST00000263735.9	c.-45_-26del		5_prime_UTR_variant	1/9	1	NM_002354.3	P1

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 6157 AN: 152062 Hom.: 402 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.0513

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.0302

GnomAD4 exome AF: 0.00577 AC: 7019 AN: 1217098 Hom.: 316 AF XY: 0.00544 AC XY: 3222 AN XY: 591888

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.0193

Gnomad4 ASJ exome AF: 0.0115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00822

Gnomad4 FIN exome AF: 0.00193

Gnomad4 NFE exome AF: 0.00141

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0406 AC: 6179 AN: 152170 Hom.: 406 Cov.: 32 AF XY: 0.0391 AC XY: 2909 AN XY: 74388

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.00179

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0247 Hom.: 26

Bravo AF: 0.0454

Asia WGS AF: 0.00984 AC: 35 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201752400; hg19: chr2-47596589;