Variant 4-154235260-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.9392C>T(p.Pro3131Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0219 in 1,613,960 control chromosomes in the GnomAD database, including 1,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.049 ( 422 hom., cov: 32)

Exomes 𝑓: 0.019 ( 1066 hom. )

Consequence

DCHS2
NM_001358235.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.68

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=0.0019030869).

BP6

Variant 4-154235260-G-A is Benign according to our data. Variant chr4-154235260-G-A is described in ClinVar as [Benign]. Clinvar id is 3059159.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 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.9392C>T	p.Pro3131Leu	missense_variant	20/20	ENST00000357232.10	NP_001345164.1
LOC101927947	XR_007058336.1 linkuse as main transcript	n.4255+28207G>A		intron_variant, non_coding_transcript_variant
LOC101927947	XR_007058335.1 linkuse as main transcript	n.689+28207G>A		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.9392C>T	p.Pro3131Leu	missense_variant	20/20	1	NM_001358235.2	ENSP00000349768	P1	Q6V1P9-1
	ENST00000660197.1 linkuse as main transcript	n.412+28207G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0493

AC:

7493

AN:

152074

Hom.:

420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0391

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0812

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00828

Gnomad OTH

AF:

0.0383

GnomAD3 exomes

AF:

0.0389

AC:

9755

AN:

250700

Hom.:

476

AF XY:

0.0367

AC XY:

4973

AN XY:

135464

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.0525

Gnomad ASJ exome

AF:

0.0172

Gnomad EAS exome

AF:

0.138

Gnomad SAS exome

AF:

0.0717

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.00748

Gnomad OTH exome

AF:

0.0239

GnomAD4 exome

AF:

0.0190

AC:

27832

AN:

1461768

Hom.:

1066

Cov.:

AF XY:

0.0200

AC XY:

14572

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0495

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.0716

Gnomad4 FIN exome

AF:

0.00236

Gnomad4 NFE exome

AF:

0.00720

Gnomad4 OTH exome

AF:

0.0325

GnomAD4 genome

AF:

0.0494

AC:

7517

AN:

152192

Hom.:

422

Cov.:

AF XY:

0.0499

AC XY:

3712

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.0390

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.0804

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00828

Gnomad4 OTH

AF:

0.0388

Alfa

AF:

0.0236

Hom.:

Bravo

AF:

0.0562

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.118

AC:

520

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.0390

AC:

4740

Asia WGS

AF:

0.113

AC:

390

AN:

3476

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

Sep 19, 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

0.18

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.054

PrimateAI

Uncertain

0.60

REVEL

Benign

0.27

MPC

0.42

ClinPred

0.039

GERP RS

4.7

gMVP

0.54

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