Variant rs2659871 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003737.4(DCHS1):c.3696G>A(p.Pro1232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,613,602 control chromosomes in the GnomAD database, including 129,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15301 hom., cov: 33)

Exomes 𝑓: 0.39 ( 114041 hom. )

Consequence

DCHS1
NM_003737.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.100

Variant links:

Genes affected

DCHS1 (HGNC:13681): (dachsous cadherin-related 1) This gene is a member of the cadherin superfamily whose members encode calcium-dependent cell-cell adhesion molecules. The encoded protein has a signal peptide, 27 cadherin repeat domains and a unique cytoplasmic region. This particular cadherin family member is expressed in fibroblasts but not in melanocytes or keratinocytes. The cell-cell adhesion of fibroblasts is thought to be necessary for wound healing. [provided by RefSeq, Jul 2008]

DCHS1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 11-6631387-C-T is Benign according to our data. Variant chr11-6631387-C-T is described in ClinVar as [Benign]. Clinvar id is 259138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6631387-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCHS1	NM_003737.4 linkuse as main transcript	c.3696G>A	p.Pro1232=	synonymous_variant	8/21	ENST00000299441.5	NP_003728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DCHS1	ENST00000299441.5 linkuse as main transcript	c.3696G>A	p.Pro1232=	synonymous_variant	8/21	1	NM_003737.4	ENSP00000299441	P1
	ENST00000656961.1 linkuse as main transcript	n.267C>T		non_coding_transcript_exon_variant	2/3
	ENST00000526633.1 linkuse as main transcript	n.168C>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

66999

AN:

151916

Hom.:

15254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.448

GnomAD3 exomes

AF:

0.409

AC:

102309

AN:

250348

Hom.:

21089

AF XY:

0.403

AC XY:

54579

AN XY:

135316

show subpopulations

Gnomad AFR exome

AF:

0.558

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.420

Gnomad EAS exome

AF:

0.448

Gnomad SAS exome

AF:

0.370

Gnomad FIN exome

AF:

0.402

Gnomad NFE exome

AF:

0.395

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.393

AC:

575044

AN:

1461568

Hom.:

114041

Cov.:

AF XY:

0.393

AC XY:

285487

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.564

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.464

Gnomad4 SAS exome

AF:

0.367

Gnomad4 FIN exome

AF:

0.397

Gnomad4 NFE exome

AF:

0.386

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.441

AC:

67095

AN:

152034

Hom.:

15301

Cov.:

AF XY:

0.439

AC XY:

32626

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.558

Gnomad4 AMR

AF:

0.414

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.455

Gnomad4 SAS

AF:

0.385

Gnomad4 FIN

AF:

0.393

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.445

Alfa

AF:

0.399

Hom.:

23646

Bravo

AF:

0.448

Asia WGS

AF:

0.413

AC:

1440

AN:

3476

EpiCase

AF:

0.382

EpiControl

AF:

0.385

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Van Maldergem syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.92

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over