Variant 4-154236578-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.8074C>T(p.Arg2692Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000777 in 1,613,936 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 2 hom. )

Consequence

DCHS2
NM_001358235.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.378

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=0.006691158).

BP6

Variant 4-154236578-G-A is Benign according to our data. Variant chr4-154236578-G-A is described in ClinVar as [Benign]. Clinvar id is 3050011.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DCHS2	NM_001358235.2 linkuse as main transcript	c.8074C>T	p.Arg2692Cys	missense_variant	20/20	ENST00000357232.10
LOC101927947	XR_007058336.1 linkuse as main transcript	n.4255+29525G>A		intron_variant, non_coding_transcript_variant
LOC101927947	XR_007058335.1 linkuse as main transcript	n.689+29525G>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.8074C>T	p.Arg2692Cys	missense_variant	20/20	1	NM_001358235.2	P1	Q6V1P9-1
	ENST00000625026.1 linkuse as main transcript	n.599G>A		non_coding_transcript_exon_variant	1/1
	ENST00000660197.1 linkuse as main transcript	n.412+29525G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00404

AC:

614

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00112

AC:

282

AN:

250800

Hom.:

AF XY:

0.000760

AC XY:

103

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000434

AC:

634

AN:

1461684

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

276

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000665

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00407

AC:

620

AN:

152252

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000776

Hom.:

Bravo

AF:

0.00462

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00138

AC:

168

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DCHS2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 19, 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

0.091

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

Cadd

Benign

7.7

Dann

Benign

0.53

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.10

MetaRNN

Benign

0.0067

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.19

REVEL

Benign

0.092

MPC

0.097

ClinPred

0.0063

GERP RS

-12

gMVP

0.074

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