Variant 4-154242632-TCA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001358235.2(DCHS2):c.7072+8_7072+9del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,604,156 control chromosomes in the GnomAD database, including 580 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.020 ( 48 hom., cov: 32)

Exomes 𝑓: 0.025 ( 532 hom. )

Consequence

DCHS2
NM_001358235.2 splice_region, intron

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.33

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 -9 ACMG points.

BP6

Variant 4-154242632-TCA-T is Benign according to our data. Variant chr4-154242632-TCA-T is described in ClinVar as [Benign]. Clinvar id is 3037465.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0201 (3067/152250) while in subpopulation NFE AF= 0.0326 (2220/68004). AF 95% confidence interval is 0.0315. There are 48 homozygotes in gnomad4. There are 1372 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
DCHS2	NM_001358235.2 linkuse as main transcript	c.7072+8_7072+9del	splice_region_variant, intron_variant	ENST00000357232.10	NP_001345164.1
LOC101927947	XR_007058336.1 linkuse as main transcript	n.4256-26426_4256-26425del	intron_variant, non_coding_transcript_variant
LOC101927947	XR_007058335.1 linkuse as main transcript	n.690-26426_690-26425del	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.7072+8_7072+9del		splice_region_variant, intron_variant		1	NM_001358235.2	ENSP00000349768	P1	Q6V1P9-1
	ENST00000660197.1 linkuse as main transcript	n.412+35583_412+35584del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

3069

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00476

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0186

AC:

4467

AN:

239960

Hom.:

AF XY:

0.0191

AC XY:

2470

AN XY:

129598

show subpopulations

Gnomad AFR exome

AF:

0.00411

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.0284

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00444

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.0290

Gnomad OTH exome

AF:

0.0198

GnomAD4 exome

AF:

0.0247

AC:

35888

AN:

1451906

Hom.:

532

AF XY:

0.0244

AC XY:

17612

AN XY:

721984

show subpopulations

Gnomad4 AFR exome

AF:

0.00356

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.0278

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00500

Gnomad4 FIN exome

AF:

0.0168

Gnomad4 NFE exome

AF:

0.0287

Gnomad4 OTH exome

AF:

0.0226

GnomAD4 genome

AF:

0.0201

AC:

3067

AN:

152250

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1372

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00474

Gnomad4 AMR

AF:

0.0186

Gnomad4 ASJ

AF:

0.0288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0155

Gnomad4 NFE

AF:

0.0326

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0292

Hom.:

Bravo

AF:

0.0193

Asia WGS

AF:

0.00346

AC:

AN:

3478

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

Dec 24, 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

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