4-154394970-T-C

Variant names:

• chr4-154394970-T-C
• rs902464
• NM_001358235.2:c.2053-17526A>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.2053-17526A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,128 control chromosomes in the GnomAD database, including 62,940 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 0.90 (62940 hom., cov: 31)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	NM_001358235.2	MANE Select	c.2053-17526A>G		intron	N/A	NP_001345164.1
	DCHS2	NM_001142552.2		c.2053-17526A>G		intron	N/A	NP_001136024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	ENST00000357232.10	TSL:1 MANE Select	c.2053-17526A>G		intron	N/A	ENSP00000349768.5
	DCHS2	ENST00000339452.2	TSL:1	c.2053-17526A>G		intron	N/A	ENSP00000345062.1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136486 AN: 152010 Hom.: 62904 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.998

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.908

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

GnomAD4 genome AF: 0.898 AC: 136577 AN: 152128 Hom.: 62940 Cov.: 31 AF XY: 0.901 AC XY: 67002 AN XY: 74370

African (AFR) AF: 0.665 AC: 27555 AN: 41454

American (AMR) AF: 0.951 AC: 14523 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3366 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5155 AN: 5164

South Asian (SAS) AF: 0.998 AC: 4808 AN: 4820

European-Finnish (FIN) AF: 0.999 AC: 10602 AN: 10612

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67469 AN: 68022

Other (OTH) AF: 0.908 AC: 1918 AN: 2112

Alfa AF: 0.949 Hom.: 118551

Bravo AF: 0.885

Asia WGS AF: 0.980 AC: 3406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.63
DANN	Benign	0.37
PhyloP100		-0.20
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: rs902464; hg19: chr4-155316122;