Variant 4-154490731-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001358235.2(DCHS2):c.625C>T(p.Pro209Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,551,632 control chromosomes in the GnomAD database, including 4,412 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.058 ( 407 hom., cov: 33)

Exomes 𝑓: 0.070 ( 4005 hom. )

Consequence

DCHS2
NM_001358235.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.800

Variant links:

Genes affected

DCHS2 (HGNC:23111): (dachsous cadherin-related 2) This gene encodes a large protein that contains many cadherin domains and likely functions in cell adhesion. Genome-wide association studies suggest that this gene may be important in Alzheimer's disease, compressive strength index, and appendicular lean mass. [provided by RefSeq, May 2017]

DCHS2 links:

DCHS2 (HGNC:):

DCHS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014812648).

BP6

Variant 4-154490731-G-A is Benign according to our data. Variant chr4-154490731-G-A is described in ClinVar as [Benign]. Clinvar id is 3059143.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCHS2	NM_001358235.2 linkuse as main transcript	c.625C>T	p.Pro209Ser	missense_variant	1/20	ENST00000357232.10	NP_001345164.1
DCHS2	NM_001142552.2 linkuse as main transcript	c.625C>T	p.Pro209Ser	missense_variant	1/8		NP_001136024.1	Q6V1P9-5A0A0A0MRC0Q6V1P8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DCHS2	ENST00000357232.10 linkuse as main transcript	c.625C>T	p.Pro209Ser	missense_variant	1/20	1	NM_001358235.2	ENSP00000349768.5	Q6V1P9-1
DCHS2	ENST00000339452.2 linkuse as main transcript	c.625C>T	p.Pro209Ser	missense_variant	1/8	1		ENSP00000345062.1	Q6V1P9-5A0A0A0MRC0
DCHS2	ENST00000456341.2 linkuse as main transcript	n.604C>T		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

AF:

0.0581

AC:

8836

AN:

152212

Hom.:

407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.0715

Gnomad ASJ

AF:

0.0360

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0283

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0764

Gnomad OTH

AF:

0.0483

GnomAD3 exomes

AF:

0.0690

AC:

10577

AN:

153180

Hom.:

557

AF XY:

0.0658

AC XY:

5358

AN XY:

81438

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.0996

Gnomad ASJ exome

AF:

0.0359

Gnomad EAS exome

AF:

0.000276

Gnomad SAS exome

AF:

0.0352

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.0721

Gnomad OTH exome

AF:

0.0593

GnomAD4 exome

AF:

0.0704

AC:

98531

AN:

1399302

Hom.:

4005

Cov.:

AF XY:

0.0692

AC XY:

47769

AN XY:

690170

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

Gnomad4 AMR exome

AF:

0.0981

Gnomad4 ASJ exome

AF:

0.0385

Gnomad4 EAS exome

AF:

0.000532

Gnomad4 SAS exome

AF:

0.0345

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.0743

Gnomad4 OTH exome

AF:

0.0580

GnomAD4 genome

AF:

0.0581

AC:

8849

AN:

152330

Hom.:

407

Cov.:

AF XY:

0.0598

AC XY:

4452

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.0718

Gnomad4 ASJ

AF:

0.0360

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.0764

Gnomad4 OTH

AF:

0.0478

Alfa

AF:

0.0657

Hom.:

542

Bravo

AF:

0.0504

TwinsUK

AF:

0.0717

AC:

266

ALSPAC

AF:

0.0651

AC:

251

ESP6500AA

AF:

0.0101

AC:

ESP6500EA

AF:

0.0817

AC:

260

ExAC

AF:

0.0454

AC:

1183

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DCHS2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.6

DANN

Benign

0.91

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.25

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

PROVEAN

Benign

0.18

.;N

REVEL

Benign

0.034

Sift

Benign

0.64

.;T

Sift4G

Benign

0.32

.;T

Vest4

0.024

ClinPred

0.0059

GERP RS

-0.34

gMVP

0.49

Splicing

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