4-154441724-T-C

Variant names:

• chr4-154441724-T-C
• rs1490683
• NM_001358235.2:c.2052+47580A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DCHS2	NM_001358235.2	c.2052+47580A>G		intron_variant	Intron 1 of 19	ENST00000357232.10	NP_001345164.1
DCHS2	NM_001142552.2	c.2052+47580A>G		intron_variant	Intron 1 of 7		NP_001136024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCHS2	ENST00000357232.10	c.2052+47580A>G		intron_variant	Intron 1 of 19	1	NM_001358235.2	ENSP00000349768.5
DCHS2	ENST00000339452.2	c.2052+47580A>G		intron_variant	Intron 1 of 7	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

African (AFR) AF: 0.0890 AC: 3103 AN: 34850

American (AMR) AF: 0.490 AC: 5383 AN: 10988

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1292 AN: 2640

East Asian (EAS) AF: 0.711 AC: 3550 AN: 4990

South Asian (SAS) AF: 0.424 AC: 1651 AN: 3892

European-Finnish (FIN) AF: 0.551 AC: 4837 AN: 8782

Middle Eastern (MID) AF: 0.377 AC: 61 AN: 162

European-Non Finnish (NFE) AF: 0.489 AC: 25284 AN: 51674

Other (OTH) AF: 0.395 AC: 604 AN: 1530

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
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1490683; hg19: chr4-155362876;