11-6634202-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003737.4(DCHS1):c.1902C>T(p.His634His) 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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.559

Publications

22 publications found

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 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), PanelApp Australia
familial mitral valve prolapse
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
van Maldergem syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DCHS1 links:

ENSG00000255410 (HGNC:):

ENSG00000255410 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 259136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
DCHS1	NM_003737.4 link	c.1902C>T	p.His634His	synonymous_variant	Exon 3 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.1902C>T	p.His634His	synonymous_variant	Exon 3 of 21	1	NM_003737.4	ENSP00000299441.3	Q96JQ0
ENSG00000255410	ENST00000526633.1 link	n.211-730G>A		intron_variant	Intron 2 of 2	3
ENSG00000255410	ENST00000656961.1 link	n.309+2773G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53661

AN:

151964

Hom.:

9694

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.373

AC:

93582

AN:

250790

AF XY:

0.373

show subpopulations

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 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.:

AF XY:

0.374

AC XY:

271614

AN XY:

726958

show subpopulations

African (AFR)

AF:

0.277

AC:

9256

AN:

33474

American (AMR)

AF:

0.352

AC:

15734

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

10670

AN:

26120

East Asian (EAS)

AF:

0.461

AC:

18288

AN:

39694

South Asian (SAS)

AF:

0.328

AC:

28240

AN:

86194

European-Finnish (FIN)

AF:

0.388

AC:

20689

AN:

53384

Middle Eastern (MID)

AF:

0.394

AC:

2269

AN:

5766

European-Non Finnish (NFE)

AF:

0.377

AC:

419249

AN:

1111692

Other (OTH)

AF:

0.369

AC:

22302

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

20620

41241

61861

82482

103102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13182

26364

39546

52728

65910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.353

AC:

53695

AN:

152084

Hom.:

9698

Cov.:

AF XY:

0.353

AC XY:

26231

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.280

AC:

11606

AN:

41482

American (AMR)

AF:

0.367

AC:

5615

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1441

AN:

3466

East Asian (EAS)

AF:

0.447

AC:

2310

AN:

5164

South Asian (SAS)

AF:

0.339

AC:

1634

AN:

4814

European-Finnish (FIN)

AF:

0.384

AC:

4063

AN:

10584

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.380

AC:

25827

AN:

67968

Other (OTH)

AF:

0.365

AC:

770

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1768

3536

5305

7073

8841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.369

Hom.:

7182

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

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

-0.51

CADD

Benign

7.5

(source)

DANN

Benign

0.85

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over