Variant 4-154373924-A-G 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.2244+3329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,597,486 control chromosomes in the GnomAD database, including 152,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.37 ( 11083 hom., cov: 28)

Exomes 𝑓: 0.44 ( 141850 hom. )

Consequence

DCHS2
NM_001358235.2 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0600

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:

ENSG00000249200 (HGNC:):

ENSG00000249200 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 (BayesDel_noAF=-0.73).

BP6

Variant 4-154373924-A-G is Benign according to our data. Variant chr4-154373924-A-G is described in ClinVar as [Benign]. Clinvar id is 3060662.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
DCHS2	NM_001358235.2 link	c.2244+3329T>C	intron_variant	ENST00000357232.10	NP_001345164.1
DCHS2	NM_001142552.2 link	c.2244+3329T>C	intron_variant		NP_001136024.1	Q6V1P9-5A0A0A0MRC0Q6V1P8
LOC100419960		n.154373924A>G	intragenic_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DCHS2	ENST00000357232.10 link	c.2244+3329T>C	intron_variant		1	NM_001358235.2	ENSP00000349768.5	Q6V1P9-1
DCHS2	ENST00000339452.2 link	c.2244+3329T>C	intron_variant		1		ENSP00000345062.1	Q6V1P9-5A0A0A0MRC0
DCHS2	ENST00000623607.4 link	n.457T>C	non_coding_transcript_exon_variant	4/25	1
ENSG00000249200	ENST00000513721.1 link	n.39A>G	non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

55142

AN:

149580

Hom.:

11084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.385

GnomAD3 exomes

AF:

0.403

AC:

98214

AN:

243854

Hom.:

20563

AF XY:

0.410

AC XY:

54091

AN XY:

131906

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.372

Gnomad SAS exome

AF:

0.432

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.444

Gnomad OTH exome

AF:

0.405

GnomAD4 exome

AF:

0.438

AC:

634801

AN:

1447792

Hom.:

141850

Cov.:

AF XY:

0.439

AC XY:

316475

AN XY:

720354

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.360

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.370

Gnomad4 SAS exome

AF:

0.435

Gnomad4 FIN exome

AF:

0.410

Gnomad4 NFE exome

AF:

0.455

Gnomad4 OTH exome

AF:

0.423

GnomAD4 genome

AF:

0.368

AC:

55152

AN:

149694

Hom.:

11083

Cov.:

AF XY:

0.371

AC XY:

27015

AN XY:

72842

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.393

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.378

Gnomad4 SAS

AF:

0.452

Gnomad4 FIN

AF:

0.423

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.382

Alfa

AF:

0.436

Hom.:

34159

Bravo

AF:

0.353

Asia WGS

AF:

0.386

AC:

1344

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

Oct 22, 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

-0.73

CADD

Benign

2.1

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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