rs1873369

chr4-154487326-C-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCHS2	NM_001358235.2	c.2052+1978G>T		intron_variant		ENST00000357232.10
DCHS2	NM_001142552.2	c.2052+1978G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCHS2	ENST00000357232.10	c.2052+1978G>T		intron_variant		1	NM_001358235.2	P1
DCHS2	ENST00000339452.2	c.2052+1978G>T		intron_variant		1
DCHS2	ENST00000456341.2	n.2032-806G>T		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.0947

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.215

Alfa AF: 0.332 Hom.: 3388

Bravo AF: 0.222

Asia WGS AF: 0.417 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.5
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1873369; hg19: chr4-155408478;