rs2659872

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003737.4(DCHS1):c.4215T>C(p.Leu1405Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,536,712 control chromosomes in the GnomAD database, including 149,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 21787 hom., cov: 34)

Exomes 𝑓: 0.43 ( 127503 hom. )

Consequence

DCHS1
NM_003737.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.702

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:

ENSG00000255410 (HGNC:):

ENSG00000255410 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 11-6630579-A-G is Benign according to our data. Variant chr11-6630579-A-G is described in ClinVar as [Benign]. Clinvar id is 259139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6630579-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.702 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCHS1	NM_003737.4 link	c.4215T>C	p.Leu1405Leu	synonymous_variant	Exon 10 of 21	ENST00000299441.5	NP_003728.1	Q96JQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DCHS1	ENST00000299441.5 link	c.4215T>C	p.Leu1405Leu	synonymous_variant	Exon 10 of 21	1	NM_003737.4	ENSP00000299441.3	Q96JQ0
ENSG00000255410	ENST00000656961.1 link	n.76A>G		non_coding_transcript_exon_variant	Exon 1 of 3
ENSG00000255410	ENST00000526633.1 link	n.-24A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78131

AN:

151848

Hom.:

21736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.747

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.434

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.504

GnomAD3 exomes

AF:

0.428

AC:

59479

AN:

138810

Hom.:

13195

AF XY:

0.425

AC XY:

32965

AN XY:

77516

show subpopulations

Gnomad AFR exome

AF:

0.737

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.425

Gnomad EAS exome

AF:

0.442

Gnomad SAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.408

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.425

AC:

588663

AN:

1384752

Hom.:

127503

Cov.:

AF XY:

0.425

AC XY:

290642

AN XY:

684366

show subpopulations

Gnomad4 AFR exome

AF:

0.758

Gnomad4 AMR exome

AF:

0.411

Gnomad4 ASJ exome

AF:

0.425

Gnomad4 EAS exome

AF:

0.466

Gnomad4 SAS exome

AF:

0.426

Gnomad4 FIN exome

AF:

0.406

Gnomad4 NFE exome

AF:

0.414

Gnomad4 OTH exome

AF:

0.438

GnomAD4 genome

AF:

0.515

AC:

78233

AN:

151960

Hom.:

21787

Cov.:

AF XY:

0.511

AC XY:

37968

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.748

Gnomad4 AMR

AF:

0.456

Gnomad4 ASJ

AF:

0.434

Gnomad4 EAS

AF:

0.460

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.401

Gnomad4 NFE

AF:

0.419

Gnomad4 OTH

AF:

0.500

Alfa

AF:

0.459

Hom.:

3132

Bravo

AF:

0.528

Asia WGS

AF:

0.458

AC:

1586

AN:

3458

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

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

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Van Maldergem syndrome 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.72

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