rs112402535

Positions:

chr11-6641235-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003737.4(DCHS1):c.379G>A(p.Val127Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00783 in 1,613,764 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 58 hom. )

Consequence

DCHS1
NM_003737.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.09

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:

ENSG00000255410 (HGNC:):

ENSG00000255410 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 (MetaRNN=0.008645952).

BP6

Variant 11-6641235-C-T is Benign according to our data. Variant chr11-6641235-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 376786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6641235-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00529 (806/152354) while in subpopulation SAS AF= 0.0108 (52/4832). AF 95% confidence interval is 0.00843. There are 2 homozygotes in gnomad4. There are 379 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCHS1	NM_003737.4 linkuse as main transcript	c.379G>A	p.Val127Ile	missense_variant	2/21	ENST00000299441.5	NP_003728.1	Q96JQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCHS1	ENST00000299441.5 linkuse as main transcript	c.379G>A	p.Val127Ile	missense_variant	2/21	1	NM_003737.4	ENSP00000299441.3		Q96JQ0
ENSG00000255410	ENST00000656961.1 linkuse as main transcript	n.309+9806C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00530

AC:

807

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0105

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00827

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00623

AC:

1560

AN:

250544

Hom.:

AF XY:

0.00672

AC XY:

911

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.00179

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00458

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0128

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.00814

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00809

AC:

11824

AN:

1461410

Hom.:

Cov.:

AF XY:

0.00811

AC XY:

5893

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.00566

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0122

Gnomad4 FIN exome

AF:

0.00192

Gnomad4 NFE exome

AF:

0.00880

Gnomad4 OTH exome

AF:

0.00828

GnomAD4 genome

AF:

0.00529

AC:

806

AN:

152354

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

379

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00828

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00805

Hom.:

Bravo

AF:

0.00570

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00273

AC:

ESP6500EA

AF:

0.00722

AC:

ExAC

AF:

0.00619

AC:

751

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00796

EpiControl

AF:

0.00782

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2018	This variant is associated with the following publications: (PMID: 30755392) -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 30, 2016	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	DCHS1: BP4, BS1, BS2 -

Hypoplasia of the corpus callosum;C0454644:Delayed speech and language development;C0557874:Global developmental delay;C1836735:Hypopigmented skin patches;C1842581:Abnormal corpus callosum morphology;C1844820:Joint hypermobility;C1849075:Relative macrocephaly;C1858120:Generalized hypotonia;C2267233:Neonatal hypotonia;C4023633:Abnormal renal pelvis morphology;C5399973:Periventricular heterotopia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Personalized Medicine, Children's Hospital Los Angeles

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0086

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.38

REVEL

Benign

0.17

Sift

Benign

0.89

Sift4G

Benign

0.26

Polyphen

0.98

Vest4

0.23

MVP

0.55

MPC

0.25

ClinPred

0.027

GERP RS

5.4

Varity_R

0.037

gMVP

0.33

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