rs2659871

Variant names:

• chr11-6631387-C-T
• rs2659871
• NM_003737.4:c.3696G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-6631387-C-T
• chr11-6631387-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003737.4(DCHS1):​c.3696G>A​(p.Pro1232Pro) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.100
• Publications: 34 publications found

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 Gene-Disease associations (from GenCC):

• mitral valve prolapse, myxomatous 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• van Maldergem syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• van Maldergem syndrome

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• familial mitral valve prolapse

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000255410 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 259138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003737.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS1	NM_003737.4	MANE Select	c.3696G>A	p.Pro1232Pro	synonymous	Exon 8 of 21	NP_003728.1	Q96JQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS1	ENST00000299441.5	TSL:1 MANE Select	c.3696G>A	p.Pro1232Pro	synonymous	Exon 8 of 21	ENSP00000299441.3	Q96JQ0
	ENSG00000255410	ENST00000526633.1	TSL:3	n.168C>T		non_coding_transcript_exon	Exon 2 of 3
	ENSG00000255410	ENST00000656961.1		n.267C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66999 AN: 151916 Hom.: 15254 Cov.: 33

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

GnomAD2 exomes AF: 0.409 AC: 102309 AN: 250348 AF XY: 0.403

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 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.: 59 AF XY: 0.393 AC XY: 285487 AN XY: 727070

African (AFR) AF: 0.564 AC: 18876 AN: 33480

American (AMR) AF: 0.398 AC: 17800 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 10902 AN: 26134

East Asian (EAS) AF: 0.464 AC: 18435 AN: 39700

South Asian (SAS) AF: 0.367 AC: 31613 AN: 86256

European-Finnish (FIN) AF: 0.397 AC: 21207 AN: 53364

Middle Eastern (MID) AF: 0.429 AC: 2473 AN: 5768

European-Non Finnish (NFE) AF: 0.386 AC: 429403 AN: 1111774

Other (OTH) AF: 0.403 AC: 24335 AN: 60368

GnomAD4 genome AF: 0.441 AC: 67095 AN: 152034 Hom.: 15301 Cov.: 33 AF XY: 0.439 AC XY: 32626 AN XY: 74328

African (AFR) AF: 0.558 AC: 23128 AN: 41458

American (AMR) AF: 0.414 AC: 6332 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1472 AN: 3468

East Asian (EAS) AF: 0.455 AC: 2347 AN: 5158

South Asian (SAS) AF: 0.385 AC: 1856 AN: 4820

European-Finnish (FIN) AF: 0.393 AC: 4153 AN: 10570

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26428 AN: 67950

Other (OTH) AF: 0.445 AC: 939 AN: 2112

Alfa AF: 0.407 Hom.: 52474

Bravo AF: 0.448

Asia WGS AF: 0.413 AC: 1440 AN: 3476

EpiCase AF: 0.382

EpiControl AF: 0.385

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Van Maldergem syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Benign	0.92
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2659871; hg19: chr11-6652618; COSMIC: COSV55030072;