Variant 4-154235390-G-A 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.9262C>T(p.His3088Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0253 in 1,613,970 control chromosomes in the GnomAD database, including 771 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.040 ( 178 hom., cov: 32)

Exomes 𝑓: 0.024 ( 593 hom. )

Consequence

DCHS2
NM_001358235.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.48

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=0.002567619).

BP6

Variant 4-154235390-G-A is Benign according to our data. Variant chr4-154235390-G-A is described in ClinVar as [Benign]. Clinvar id is 3056142.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DCHS2	NM_001358235.2 linkuse as main transcript	c.9262C>T	p.His3088Tyr	missense_variant	20/20	ENST00000357232.10
LOC101927947	XR_007058336.1 linkuse as main transcript	n.4255+28337G>A		intron_variant, non_coding_transcript_variant
LOC101927947	XR_007058335.1 linkuse as main transcript	n.689+28337G>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.9262C>T	p.His3088Tyr	missense_variant	20/20	1	NM_001358235.2	P1	Q6V1P9-1
	ENST00000660197.1 linkuse as main transcript	n.412+28337G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0403

AC:

6126

AN:

152076

Hom.:

176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0826

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0494

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.0472

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0219

Gnomad OTH

AF:

0.0445

GnomAD3 exomes

AF:

0.0271

AC:

6792

AN:

250796

Hom.:

149

AF XY:

0.0237

AC XY:

3218

AN XY:

135520

show subpopulations

Gnomad AFR exome

AF:

0.0812

Gnomad AMR exome

AF:

0.0462

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.0426

Gnomad SAS exome

AF:

0.00225

Gnomad FIN exome

AF:

0.00397

Gnomad NFE exome

AF:

0.0223

Gnomad OTH exome

AF:

0.0322

GnomAD4 exome

AF:

0.0238

AC:

34754

AN:

1461776

Hom.:

593

Cov.:

AF XY:

0.0226

AC XY:

16443

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0841

Gnomad4 AMR exome

AF:

0.0469

Gnomad4 ASJ exome

AF:

0.0203

Gnomad4 EAS exome

AF:

0.0625

Gnomad4 SAS exome

AF:

0.00240

Gnomad4 FIN exome

AF:

0.00440

Gnomad4 NFE exome

AF:

0.0221

Gnomad4 OTH exome

AF:

0.0266

GnomAD4 genome

AF:

0.0403

AC:

6134

AN:

152194

Hom.:

178

Cov.:

AF XY:

0.0387

AC XY:

2877

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0826

Gnomad4 AMR

AF:

0.0492

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.0473

Gnomad4 SAS

AF:

0.00312

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.0219

Gnomad4 OTH

AF:

0.0449

Alfa

AF:

0.0258

Hom.:

107

Bravo

AF:

0.0447

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0192

AC:

ESP6500AA

AF:

0.0826

AC:

364

ESP6500EA

AF:

0.0202

AC:

174

ExAC

AF:

0.0276

AC:

3355

Asia WGS

AF:

0.0440

AC:

153

AN:

3478

EpiCase

AF:

0.0205

EpiControl

AF:

0.0216

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

Aug 08, 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

0.081

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.2

MutationTaster

Benign

0.98

PrimateAI

Benign

0.36

REVEL

Benign

0.17

MPC

0.35

ClinPred

0.035

GERP RS

5.5

gMVP

0.27

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