rs2659869

Variant names:

• chr11-6634101-T-A
• rs2659869
• NM_003737.4:c.1986+17A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-6634101-T-A
• chr11-6634101-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.902

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]

ENSG00000255410 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
DCHS1	NM_003737.4	c.1986+17A>T		intron_variant	Intron 3 of 20	ENST00000299441.5	NP_003728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCHS1	ENST00000299441.5	c.1986+17A>T		intron_variant	Intron 3 of 20	1	NM_003737.4	ENSP00000299441.3
ENSG00000255410	ENST00000526633.1	n.211-831T>A		intron_variant	Intron 2 of 2	3
ENSG00000255410	ENST00000656961.1	n.309+2672T>A		intron_variant	Intron 2 of 2
DCHS1	ENST00000680123.1	n.-211A>T		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58943 AN: 151922 Hom.: 11534 Cov.: 32

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

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.: 50 AF XY: 0.376 AC XY: 269584 AN XY: 716386

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.: 32 AF XY: 0.386 AC XY: 28714 AN XY: 74312

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

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

- -

Jul 06, 2018

GeneDx

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

- -

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	-0.92
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

Other links and lift over

dbSNP: rs2659869; hg19: chr11-6655332; COSMIC: COSV55037231;