Variant rs2659869 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003737.4(DCHS1):c.1986+17A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,597,090 control chromosomes in the GnomAD database, including 114,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11552 hom., cov: 32)

Exomes 𝑓: 0.38 ( 103269 hom. )

Consequence

DCHS1
NM_003737.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.902

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 11-6634101-T-A is Benign according to our data. Variant chr11-6634101-T-A is described in ClinVar as [Benign]. Clinvar id is 259137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6634101-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 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.1986+17A>T		intron_variant		ENST00000299441.5	NP_003728.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
DCHS1	ENST00000299441.5 linkuse as main transcript	c.1986+17A>T	intron_variant	1	NM_003737.4	ENSP00000299441	P1
	ENST00000656961.1 linkuse as main transcript	n.309+2672T>A	intron_variant, non_coding_transcript_variant
	ENST00000526633.1 linkuse as main transcript	n.211-831T>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58943

AN:

151922

Hom.:

11534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.393

GnomAD3 exomes

AF:

0.381

AC:

91529

AN:

240188

Hom.:

17432

AF XY:

0.379

AC XY:

48890

AN XY:

129136

show subpopulations

Gnomad AFR exome

AF:

0.397

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.408

Gnomad EAS exome

AF:

0.447

Gnomad SAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.377

AC:

545182

AN:

1445048

Hom.:

103269

Cov.:

AF XY:

0.376

AC XY:

269584

AN XY:

716386

show subpopulations

Gnomad4 AFR exome

AF:

0.400

Gnomad4 AMR exome

AF:

0.357

Gnomad4 ASJ exome

AF:

0.409

Gnomad4 EAS exome

AF:

0.461

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.377

Gnomad4 OTH exome

AF:

0.377

GnomAD4 genome

AF:

0.388

AC:

59002

AN:

152042

Hom.:

11552

Cov.:

AF XY:

0.386

AC XY:

28714

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.401

Gnomad4 AMR

AF:

0.381

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.448

Gnomad4 SAS

AF:

0.341

Gnomad4 FIN

AF:

0.384

Gnomad4 NFE

AF:

0.380

Gnomad4 OTH

AF:

0.390

Alfa

AF:

0.316

Hom.:

1346

Bravo

AF:

0.387

Asia WGS

AF:

0.372

AC:

1296

AN:

3478

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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic 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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

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

-0.92

CADD

Benign

5.1

DANN

Benign

0.59

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