rs7672337

Positions:

• chr4-154330458-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358235.2(DCHS2):​c.3731-748T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,044 control chromosomes in the GnomAD database, including 9,964 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 0.36 (9964 hom., cov: 31)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCHS2	NM_001358235.2	c.3731-748T>C		intron_variant		ENST00000357232.10	NP_001345164.1
DCHS2	NM_001142552.2	c.3731-748T>C		intron_variant			NP_001136024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCHS2	ENST00000357232.10	c.3731-748T>C		intron_variant		1	NM_001358235.2	ENSP00000349768	P1
DCHS2	ENST00000339452.2	c.3731-748T>C		intron_variant		1		ENSP00000345062
DCHS2	ENST00000623607.4	n.2365-748T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53963 AN: 151926 Hom.: 9959 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.355 AC: 53993 AN: 152044 Hom.: 9964 Cov.: 31 AF XY: 0.353 AC XY: 26239 AN XY: 74304

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.357

Alfa AF: 0.387 Hom.: 5067

Bravo AF: 0.348

Asia WGS AF: 0.266 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7672337; hg19: chr4-155251610;