rs747578954

Positions:

• chr2-47386566-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002354.3(EPCAM):​c.904-6T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000228 in 1,446,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: EPCAM NM_002354.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.007497
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-47386566-T-C is Benign according to our data. Variant chr2-47386566-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 219971.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPCAM	NM_002354.3	c.904-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000263735.9	NP_002345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000263735.9	c.904-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002354.3	ENSP00000263735	P1
EPCAM	ENST00000405271.5	c.988-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000385476
EPCAM	ENST00000456133.5	c.988-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000410675

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 249698 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000228 AC: 33 AN: 1446530 Hom.: 0 Cov.: 27 AF XY: 0.0000195 AC XY: 14 AN XY: 719744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000291

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000301 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 15, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0075
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.39		Position offset: 6

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

Publications

LitVar

Other links and lift over

dbSNP: rs747578954; hg19: chr2-47613705;