4-154353908-G-A

Variant names:

• chr4-154353908-G-A
• rs13138970
• NM_001358235.2:c.2476+12302C>T

Variant summary

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

The NM_001358235.2(DCHS2):​c.2476+12302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,074 control chromosomes in the GnomAD database, including 8,481 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 0.30 (8481 hom., cov: 33)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635

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 (NFE) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCHS2	NM_001358235.2	c.2476+12302C>T		intron_variant	Intron 3 of 19	ENST00000357232.10	NP_001345164.1
DCHS2	NM_001142552.2	c.2476+12302C>T		intron_variant	Intron 3 of 7		NP_001136024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCHS2	ENST00000357232.10	c.2476+12302C>T		intron_variant	Intron 3 of 19	1	NM_001358235.2	ENSP00000349768.5

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45874 AN: 151958 Hom.: 8485 Cov.: 33

Gnomad AFR AF: 0.0824

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.301 AC: 45850 AN: 152074 Hom.: 8481 Cov.: 33 AF XY: 0.303 AC XY: 22535 AN XY: 74322

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.324

Alfa AF: 0.353 Hom.: 4611

Bravo AF: 0.286

Asia WGS AF: 0.219 AC: 768 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	1.2
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs13138970; hg19: chr4-155275060;