rs1873369

Variant names:

• chr4-154487326-C-A
• rs1873369
• NM_001358235.2:c.2052+1978G>T

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+1978G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,146 control chromosomes in the GnomAD database, including 4,941 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 0.23 (4941 hom., cov: 33)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 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+1978G>T		intron	N/A	NP_001345164.1	Q6V1P9-1
	DCHS2	NM_001142552.2		c.2052+1978G>T		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+1978G>T		intron	N/A	ENSP00000349768.5	Q6V1P9-1
	DCHS2	ENST00000339452.2	TSL:1	c.2052+1978G>T		intron	N/A	ENSP00000345062.1	Q6V1P9-5
	DCHS2	ENST00000456341.2	TSL:1	n.2032-806G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34339 AN: 152028 Hom.: 4938 Cov.: 33

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.226 AC: 34348 AN: 152146 Hom.: 4941 Cov.: 33 AF XY: 0.234 AC XY: 17404 AN XY: 74346

African (AFR) AF: 0.0947 AC: 3934 AN: 41540

American (AMR) AF: 0.281 AC: 4299 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3470

East Asian (EAS) AF: 0.660 AC: 3408 AN: 5164

South Asian (SAS) AF: 0.292 AC: 1404 AN: 4814

European-Finnish (FIN) AF: 0.330 AC: 3489 AN: 10572

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16132 AN: 67984

Other (OTH) AF: 0.215 AC: 454 AN: 2114

Alfa AF: 0.312 Hom.: 3674

Bravo AF: 0.222

Asia WGS AF: 0.417 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.5
DANN	Benign	0.74
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1873369;

hg19: chr4-155408478;