Variant 4-154235863-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001358235.2(DCHS2):c.8789A>G(p.Lys2930Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 1,614,038 control chromosomes in the GnomAD database, including 3,304 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 (no stars).

Frequency

Genomes: 𝑓 0.058 ( 554 hom., cov: 32)

Exomes 𝑓: 0.033 ( 2750 hom. )

Consequence

DCHS2
NM_001358235.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.500

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031683743).

BP6

Variant 4-154235863-T-C is Benign according to our data. Variant chr4-154235863-T-C is described in ClinVar as [Benign]. Clinvar id is 3059711.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DCHS2	NM_001358235.2 linkuse as main transcript	c.8789A>G	p.Lys2930Arg	missense_variant	20/20	ENST00000357232.10	NP_001345164.1
LOC101927947	XR_007058336.1 linkuse as main transcript	n.4255+28810T>C		intron_variant, non_coding_transcript_variant
LOC101927947	XR_007058335.1 linkuse as main transcript	n.689+28810T>C		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.8789A>G	p.Lys2930Arg	missense_variant	20/20	1	NM_001358235.2	ENSP00000349768	P1	Q6V1P9-1
	ENST00000660197.1 linkuse as main transcript	n.412+28810T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0581

AC:

8839

AN:

152158

Hom.:

553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0861

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.0814

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00329

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0223

Gnomad OTH

AF:

0.0674

GnomAD3 exomes

AF:

0.0651

AC:

16290

AN:

250344

Hom.:

1842

AF XY:

0.0527

AC XY:

7142

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.0856

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.0750

Gnomad SAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.00397

Gnomad NFE exome

AF:

0.0224

Gnomad OTH exome

AF:

0.0631

GnomAD4 exome

AF:

0.0326

AC:

47595

AN:

1461762

Hom.:

2750

Cov.:

AF XY:

0.0302

AC XY:

21942

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0866

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.0204

Gnomad4 EAS exome

AF:

0.0941

Gnomad4 SAS exome

AF:

0.00333

Gnomad4 FIN exome

AF:

0.00442

Gnomad4 NFE exome

AF:

0.0223

Gnomad4 OTH exome

AF:

0.0343

GnomAD4 genome

AF:

0.0581

AC:

8850

AN:

152276

Hom.:

554

Cov.:

AF XY:

0.0591

AC XY:

4404

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0860

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.0809

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00329

Gnomad4 NFE

AF:

0.0223

Gnomad4 OTH

AF:

0.0676

Alfa

AF:

0.0338

Hom.:

389

Bravo

AF:

0.0746

TwinsUK

AF:

0.0224

AC:

ALSPAC

AF:

0.0192

AC:

ESP6500AA

AF:

0.0860

AC:

379

ESP6500EA

AF:

0.0207

AC:

178

ExAC

AF:

0.0558

AC:

6770

Asia WGS

AF:

0.0610

AC:

210

AN:

3478

EpiCase

AF:

0.0207

EpiControl

AF:

0.0220

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

May 28, 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

0.079

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.85

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

REVEL

Benign

0.041

MPC

0.060

ClinPred

0.0046

GERP RS

0.79

gMVP

0.071

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