Variant 4-154236719-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001358235.2(DCHS2):c.7933T>C(p.Leu2645=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,613,906 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0077 ( 8 hom., cov: 32)

Exomes 𝑓: 0.012 ( 111 hom. )

Consequence

DCHS2
NM_001358235.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.318

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 (BayesDel_noAF=-0.87).

BP6

Variant 4-154236719-A-G is Benign according to our data. Variant chr4-154236719-A-G is described in ClinVar as [Benign]. Clinvar id is 3038093.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.318 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DCHS2	NM_001358235.2 linkuse as main transcript	c.7933T>C	p.Leu2645=	synonymous_variant	20/20	ENST00000357232.10	NP_001345164.1
LOC101927947	XR_007058336.1 linkuse as main transcript	n.4255+29666A>G		intron_variant, non_coding_transcript_variant
LOC101927947	XR_007058335.1 linkuse as main transcript	n.689+29666A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCHS2	ENST00000357232.10 linkuse as main transcript	c.7933T>C	p.Leu2645=	synonymous_variant	20/20	1	NM_001358235.2	ENSP00000349768	P1	Q6V1P9-1
	ENST00000625026.1 linkuse as main transcript	n.740A>G		non_coding_transcript_exon_variant	1/1
	ENST00000660197.1 linkuse as main transcript	n.412+29666A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00767

AC:

1167

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00910

Gnomad ASJ

AF:

0.00664

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00848

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00776

AC:

1942

AN:

250260

Hom.:

AF XY:

0.00793

AC XY:

1072

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00646

Gnomad ASJ exome

AF:

0.00647

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00248

Gnomad FIN exome

AF:

0.00802

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.00920

GnomAD4 exome

AF:

0.0115

AC:

16811

AN:

1461598

Hom.:

111

Cov.:

AF XY:

0.0112

AC XY:

8154

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00698

Gnomad4 ASJ exome

AF:

0.00677

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00234

Gnomad4 FIN exome

AF:

0.0100

Gnomad4 NFE exome

AF:

0.0134

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.00766

AC:

1167

AN:

152308

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

540

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00241

Gnomad4 AMR

AF:

0.00909

Gnomad4 ASJ

AF:

0.00664

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00848

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00973

Hom.:

Bravo

AF:

0.00804

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0111

EpiControl

AF:

0.0133

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

Feb 27, 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

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

DANN

Benign

0.59

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