rs997263

chr11-6634202-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003737.4(DCHS1):c.1902C>T(p.His634=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,613,462 control chromosomes in the GnomAD database, including 112,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9698 hom., cov: 33)
  • Exomes 𝑓: 0.37 (102858 hom.)
• Consequence: DCHS1 NM_003737.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.559

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 11-6634202-G-A is Benign according to our data. Variant chr11-6634202-G-A is described in ClinVar as [Benign]. Clinvar id is 259136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6634202-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.559 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCHS1	NM_003737.4	c.1902C>T	p.His634=	synonymous_variant	3/21	ENST00000299441.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCHS1	ENST00000299441.5	c.1902C>T	p.His634=	synonymous_variant	3/21	1	NM_003737.4	P1
	ENST00000656961.1	n.309+2773G>A		intron_variant, non_coding_transcript_variant
	ENST00000526633.1	n.211-730G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53661 AN: 151964 Hom.: 9694 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.367

GnomAD3 exomes AF: 0.373 AC: 93582 AN: 250790 Hom.: 17502 AF XY: 0.373 AC XY: 50507 AN XY: 135510

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.352

Gnomad ASJ exome AF: 0.411

Gnomad EAS exome AF: 0.447

Gnomad SAS exome AF: 0.328

Gnomad FIN exome AF: 0.393

Gnomad NFE exome AF: 0.385

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.374 AC: 546697 AN: 1461378 Hom.: 102858 Cov.: 58 AF XY: 0.374 AC XY: 271614 AN XY: 726958

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.353 AC: 53695 AN: 152084 Hom.: 9698 Cov.: 33 AF XY: 0.353 AC XY: 26231 AN XY: 74334

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.365

Alfa AF: 0.370 Hom.: 5734

Bravo AF: 0.347

Asia WGS AF: 0.363 AC: 1267 AN: 3478

EpiCase AF: 0.373

EpiControl AF: 0.375

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

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:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	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	-0.51
Cadd	Benign	7.5
Dann	Benign	0.85

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: rs997263; hg19: chr11-6655433; COSMIC: COSV55037241;