4-154458731-A-G

Variant names:

• chr4-154458731-A-G
• rs11731813
• NM_001358235.2:c.2052+30573T>C

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+30573T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,128 control chromosomes in the GnomAD database, including 4,871 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 0.22 (4871 hom., cov: 33)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358235.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	NM_001358235.2	MANE Select	c.2052+30573T>C		intron	N/A	NP_001345164.1	Q6V1P9-1
	DCHS2	NM_001142552.2		c.2052+30573T>C		intron	N/A	NP_001136024.1	Q6V1P9-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	ENST00000357232.10	TSL:1 MANE Select	c.2052+30573T>C		intron	N/A	ENSP00000349768.5	Q6V1P9-1
	DCHS2	ENST00000339452.2	TSL:1	c.2052+30573T>C		intron	N/A	ENSP00000345062.1	Q6V1P9-5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33985 AN: 152010 Hom.: 4869 Cov.: 33

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.223 AC: 33995 AN: 152128 Hom.: 4871 Cov.: 33 AF XY: 0.231 AC XY: 17144 AN XY: 74336

African (AFR) AF: 0.0923 AC: 3833 AN: 41528

American (AMR) AF: 0.273 AC: 4177 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 899 AN: 3466

East Asian (EAS) AF: 0.654 AC: 3384 AN: 5172

South Asian (SAS) AF: 0.251 AC: 1213 AN: 4828

European-Finnish (FIN) AF: 0.330 AC: 3489 AN: 10562

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16240 AN: 67980

Other (OTH) AF: 0.204 AC: 431 AN: 2110

Alfa AF: 0.227 Hom.: 9464

Bravo AF: 0.219

Asia WGS AF: 0.397 AC: 1378 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.8
DANN	Benign	0.77
PhyloP100		1.1
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: rs11731813; hg19: chr4-155379883;