4-154441724-T-C

Position:

• chr4-154441724-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.2052+47580A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 120,320 control chromosomes in the GnomAD database, including 8,872 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 0.38 (8872 hom., cov: 31)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCHS2	NM_001358235.2	c.2052+47580A>G		intron_variant		ENST00000357232.10	NP_001345164.1
DCHS2	NM_001142552.2	c.2052+47580A>G		intron_variant			NP_001136024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCHS2	ENST00000357232.10	c.2052+47580A>G		intron_variant		1	NM_001358235.2	ENSP00000349768.5
DCHS2	ENST00000339452.2	c.2052+47580A>G		intron_variant		1		ENSP00000345062.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 46222 AN: 120184 Hom.: 8871 Cov.: 31

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.384 AC: 46240 AN: 120320 Hom.: 8872 Cov.: 31 AF XY: 0.391 AC XY: 23123 AN XY: 59164

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.395

Alfa AF: 0.344 Hom.: 1213

Bravo AF: 0.294

Asia WGS AF: 0.469 AC: 1623 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1490683; hg19: chr4-155362876;