Variant 4-154235055-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001358235.2(DCHS2):c.9597C>T(p.Asp3199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 1,613,736 control chromosomes in the GnomAD database, including 642,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.74 ( 45892 hom., cov: 31)

Exomes 𝑓: 0.90 ( 596590 hom. )

Consequence

DCHS2
NM_001358235.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.413

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-154235055-G-A is Benign according to our data. Variant chr4-154235055-G-A is described in ClinVar as [Benign]. Clinvar id is 3059022.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.413 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DCHS2	NM_001358235.2 linkuse as main transcript	c.9597C>T	p.Asp3199=	synonymous_variant	20/20	ENST00000357232.10
LOC101927947	XR_007058336.1 linkuse as main transcript	n.4255+28002G>A		intron_variant, non_coding_transcript_variant
LOC101927947	XR_007058335.1 linkuse as main transcript	n.689+28002G>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.9597C>T	p.Asp3199=	synonymous_variant	20/20	1	NM_001358235.2	P1	Q6V1P9-1
	ENST00000660197.1 linkuse as main transcript	n.412+28002G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.736

AC:

111780

AN:

151960

Hom.:

45889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.925

Gnomad AMR

AF:

0.669

Gnomad ASJ

AF:

0.917

Gnomad EAS

AF:

0.771

Gnomad SAS

AF:

0.897

Gnomad FIN

AF:

0.967

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.922

Gnomad OTH

AF:

0.731

GnomAD3 exomes

AF:

0.830

AC:

207967

AN:

250542

Hom.:

90111

AF XY:

0.852

AC XY:

115307

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.599

Gnomad ASJ exome

AF:

0.907

Gnomad EAS exome

AF:

0.785

Gnomad SAS exome

AF:

0.907

Gnomad FIN exome

AF:

0.967

Gnomad NFE exome

AF:

0.922

Gnomad OTH exome

AF:

0.847

GnomAD4 exome

AF:

0.897

AC:

1310699

AN:

1461658

Hom.:

596590

Cov.:

100

AF XY:

0.900

AC XY:

654267

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.330

Gnomad4 AMR exome

AF:

0.606

Gnomad4 ASJ exome

AF:

0.909

Gnomad4 EAS exome

AF:

0.789

Gnomad4 SAS exome

AF:

0.905

Gnomad4 FIN exome

AF:

0.966

Gnomad4 NFE exome

AF:

0.927

Gnomad4 OTH exome

AF:

0.863

GnomAD4 genome

AF:

0.735

AC:

111804

AN:

152078

Hom.:

45892

Cov.:

AF XY:

0.740

AC XY:

54981

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.350

Gnomad4 AMR

AF:

0.669

Gnomad4 ASJ

AF:

0.917

Gnomad4 EAS

AF:

0.771

Gnomad4 SAS

AF:

0.898

Gnomad4 FIN

AF:

0.967

Gnomad4 NFE

AF:

0.922

Gnomad4 OTH

AF:

0.731

Alfa

AF:

0.877

Hom.:

95351

Bravo

AF:

0.694

Asia WGS

AF:

0.794

AC:

2764

AN:

3476

EpiCase

AF:

0.921

EpiControl

AF:

0.915

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

Oct 17, 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

-0.80

CADD

Benign

0.14

DANN

Benign

0.23

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