rs12504201

chr4-154437535-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+51769G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,034 control chromosomes in the GnomAD database, including 8,948 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 0.31 (8948 hom., cov: 32)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCHS2	NM_001358235.2	c.2052+51769G>T		intron_variant		ENST00000357232.10
DCHS2	NM_001142552.2	c.2052+51769G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCHS2	ENST00000357232.10	c.2052+51769G>T		intron_variant		1	NM_001358235.2	P1
DCHS2	ENST00000339452.2	c.2052+51769G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46570 AN: 151916 Hom.: 8947 Cov.: 32

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.306 AC: 46589 AN: 152034 Hom.: 8948 Cov.: 32 AF XY: 0.314 AC XY: 23306 AN XY: 74290

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.286

Alfa AF: 0.354 Hom.: 2086

Bravo AF: 0.295

Asia WGS AF: 0.470 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.2
Dann	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12504201; hg19: chr4-155358687;