rs12649437

Positions:

• chr4-154466019-A-G
• chr4-154466019-A-T

Variant summary

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

The NM_001358235.2(DCHS2):​c.2052+23285T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,048 control chromosomes in the GnomAD database, including 5,155 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 0.26 (5155 hom., cov: 31)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCHS2	NM_001358235.2	c.2052+23285T>C		intron_variant		ENST00000357232.10
DCHS2	NM_001142552.2	c.2052+23285T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCHS2	ENST00000357232.10	c.2052+23285T>C		intron_variant		1	NM_001358235.2	P1
DCHS2	ENST00000339452.2	c.2052+23285T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38909 AN: 151932 Hom.: 5157 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.256 AC: 38910 AN: 152048 Hom.: 5155 Cov.: 31 AF XY: 0.254 AC XY: 18854 AN XY: 74330

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.267

Alfa AF: 0.285 Hom.: 2918

Bravo AF: 0.248

Asia WGS AF: 0.254 AC: 883 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12649437; hg19: chr4-155387171;