4-154394970-T-C

Position:

• chr4-154394970-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358235.2(DCHS2):​c.2053-17526A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,128 control chromosomes in the GnomAD database, including 62,940 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (62940 hom., cov: 31)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCHS2	NM_001358235.2	c.2053-17526A>G		intron_variant		ENST00000357232.10	NP_001345164.1
DCHS2	NM_001142552.2	c.2053-17526A>G		intron_variant			NP_001136024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCHS2	ENST00000357232.10	c.2053-17526A>G		intron_variant		1	NM_001358235.2	ENSP00000349768.5
DCHS2	ENST00000339452.2	c.2053-17526A>G		intron_variant		1		ENSP00000345062.1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136486 AN: 152010 Hom.: 62904 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.998

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.908

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.898 AC: 136577 AN: 152128 Hom.: 62940 Cov.: 31 AF XY: 0.901 AC XY: 67002 AN XY: 74370

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.971

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.998

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.992

Gnomad4 OTH AF: 0.908

Alfa AF: 0.977 Hom.: 68526

Bravo AF: 0.885

Asia WGS AF: 0.980 AC: 3406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.63
DANN	Benign	0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs902464; hg19: chr4-155316122;