4-5628743-TAA-TA

Variant names:

• chr4-5628743-TA-T
• rs35103377
• NM_147127.5:c.1711-10delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_147127.5(EVC2):​c.1711-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8930 hom., cov: 0)
  • Exomes 𝑓: 0.32 (44029 hom.)
• Consequence: EVC2 NM_147127.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.151
• Publications: 4 publications found

Genes affected

EVC2 (HGNC:19747): (EvC ciliary complex subunit 2) This gene encodes a protein that functions in bone formation and skeletal development. Mutations in this gene, as well as in a neighboring gene that lies in a head-to-head configuration, cause Ellis-van Creveld syndrome, an autosomal recessive skeletal dysplasia that is also known as chondroectodermal dysplasia. Mutations in this gene also cause acrofacial dysostosis Weyers type, also referred to as Curry-Hall syndrome, a disease that combines limb and facial abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

EVC2 Gene-Disease associations (from GenCC):

• acrofacial dysostosis, Weyers type

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• Ellis-van Creveld syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 4-5628743-TA-T is Benign according to our data. Variant chr4-5628743-TA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1168070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC2	NM_147127.5	c.1711-10delT		intron_variant	Intron 11 of 21	ENST00000344408.10	NP_667338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC2	ENST00000344408.10	c.1711-10delT		intron_variant	Intron 11 of 21	1	NM_147127.5	ENSP00000342144.5
EVC2	ENST00000310917.6	c.1471-10delT		intron_variant	Intron 11 of 21	1		ENSP00000311683.2
EVC2	ENST00000475313.5	n.1471-10delT		intron_variant	Intron 11 of 22	1		ENSP00000431981.1
EVC2	ENST00000509670.1	n.*104-10delT		intron_variant	Intron 12 of 22	1		ENSP00000423876.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 49509 AN: 148518 Hom.: 8910 Cov.: 0

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.309

GnomAD2 exomes AF: 0.409 AC: 76853 AN: 187796 AF XY: 0.401

Gnomad AFR exome AF: 0.480

Gnomad AMR exome AF: 0.504

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.655

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.388

GnomAD4 exome AF: 0.316 AC: 378436 AN: 1199090 Hom.: 44029 Cov.: 0 AF XY: 0.315 AC XY: 187736 AN XY: 595598

African (AFR) AF: 0.453 AC: 14274 AN: 31478

American (AMR) AF: 0.459 AC: 17538 AN: 38196

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 6443 AN: 20602

East Asian (EAS) AF: 0.620 AC: 21766 AN: 35098

South Asian (SAS) AF: 0.334 AC: 22915 AN: 68672

European-Finnish (FIN) AF: 0.324 AC: 14179 AN: 43810

Middle Eastern (MID) AF: 0.283 AC: 1365 AN: 4818

European-Non Finnish (NFE) AF: 0.291 AC: 263456 AN: 906840

Other (OTH) AF: 0.333 AC: 16500 AN: 49576

GnomAD4 genome AF: 0.334 AC: 49569 AN: 148626 Hom.: 8930 Cov.: 0 AF XY: 0.337 AC XY: 24433 AN XY: 72424

African (AFR) AF: 0.446 AC: 18251 AN: 40924

American (AMR) AF: 0.386 AC: 5777 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 899 AN: 3412

East Asian (EAS) AF: 0.615 AC: 3128 AN: 5090

South Asian (SAS) AF: 0.292 AC: 1359 AN: 4648

European-Finnish (FIN) AF: 0.295 AC: 2850 AN: 9676

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.246 AC: 16421 AN: 66672

Other (OTH) AF: 0.306 AC: 626 AN: 2048

Alfa AF: 0.216 Hom.: 399

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 13, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 07, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs35103377; hg19: chr4-5630470; COSMIC: COSV60388092;