Variant 4-154240735-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001358235.2(DCHS2):c.7161T>C(p.Ser2387=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.007 in 1,613,926 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0064 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 60 hom. )

Consequence

DCHS2
NM_001358235.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.00500

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=-0.76).

BP6

Variant 4-154240735-A-G is Benign according to our data. Variant chr4-154240735-A-G is described in ClinVar as [Benign]. Clinvar id is 3039121.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.005 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00706 (10325/1461676) while in subpopulation MID AF= 0.0253 (146/5764). AF 95% confidence interval is 0.022. There are 60 homozygotes in gnomad4_exome. There are 5287 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DCHS2	NM_001358235.2 linkuse as main transcript	c.7161T>C	p.Ser2387=	synonymous_variant	18/20	ENST00000357232.10	NP_001345164.1
LOC101927947	XR_007058336.1 linkuse as main transcript	n.4256-28327A>G		intron_variant, non_coding_transcript_variant
LOC101927947	XR_007058335.1 linkuse as main transcript	n.690-28327A>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.7161T>C	p.Ser2387=	synonymous_variant	18/20	1	NM_001358235.2	ENSP00000349768	P1	Q6V1P9-1
	ENST00000660197.1 linkuse as main transcript	n.412+33682A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00641

AC:

975

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00856

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00701

AC:

1761

AN:

251064

Hom.:

AF XY:

0.00744

AC XY:

1010

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00657

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00506

Gnomad FIN exome

AF:

0.00203

Gnomad NFE exome

AF:

0.00886

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00706

AC:

10325

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00727

AC XY:

5287

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.00758

Gnomad4 ASJ exome

AF:

0.0238

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00493

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.00726

Gnomad4 OTH exome

AF:

0.00906

GnomAD4 genome

AF:

0.00640

AC:

974

AN:

152250

Hom.:

Cov.:

AF XY:

0.00591

AC XY:

440

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00664

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00856

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00762

Hom.:

Bravo

AF:

0.00736

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.0118

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

Mar 15, 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

-0.76

CADD

Benign

1.4

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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