Variant 4-154235446-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001358235.2(DCHS2):c.9206C>T(p.Pro3069Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000978 in 1,613,990 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 14 hom. )

Consequence

DCHS2
NM_001358235.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.07

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004939884).

BP6

Variant 4-154235446-G-A is Benign according to our data. Variant chr4-154235446-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038479.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DCHS2	NM_001358235.2 linkuse as main transcript	c.9206C>T	p.Pro3069Leu	missense_variant	20/20	ENST00000357232.10
LOC101927947	XR_007058336.1 linkuse as main transcript	n.4255+28393G>A		intron_variant, non_coding_transcript_variant
LOC101927947	XR_007058335.1 linkuse as main transcript	n.689+28393G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCHS2	ENST00000357232.10 linkuse as main transcript	c.9206C>T	p.Pro3069Leu	missense_variant	20/20	1	NM_001358235.2	P1	Q6V1P9-1
	ENST00000660197.1 linkuse as main transcript	n.412+28393G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000953

AC:

145

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00149

AC:

374

AN:

250564

Hom.:

AF XY:

0.00148

AC XY:

200

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000840

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.000981

AC:

1434

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

732

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.0186

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000555

Gnomad4 OTH exome

AF:

0.00263

GnomAD4 genome

AF:

0.000953

AC:

145

AN:

152198

Hom.:

Cov.:

AF XY:

0.000820

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00117

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00137

AC:

166

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DCHS2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 18, 2022

This variant is classified as likely 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

0.088

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Benign

0.96

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.69

M_CAP

Benign

0.0089

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.90

MutationTaster

Benign

0.90

PrimateAI

Benign

0.36

REVEL

Benign

0.21

MPC

0.39

ClinPred

0.045

GERP RS

5.8

gMVP

0.41

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