rs12649437

Variant names:

• chr4-154466019-A-G
• rs12649437
• NM_001358235.2:c.2052+23285T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.87).
• 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 rank	MANE	Protein	UniProt
DCHS2	NM_001358235.2	c.2052+23285T>C		intron_variant	Intron 1 of 19	ENST00000357232.10	NP_001345164.1
DCHS2	NM_001142552.2	c.2052+23285T>C		intron_variant	Intron 1 of 7		NP_001136024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCHS2	ENST00000357232.10	c.2052+23285T>C		intron_variant	Intron 1 of 19	1	NM_001358235.2	ENSP00000349768.5
DCHS2	ENST00000339452.2	c.2052+23285T>C		intron_variant	Intron 1 of 7	1		ENSP00000345062.1

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

African (AFR) AF: 0.203 AC: 8433 AN: 41514

American (AMR) AF: 0.214 AC: 3265 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3470

East Asian (EAS) AF: 0.190 AC: 981 AN: 5166

South Asian (SAS) AF: 0.309 AC: 1486 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2761 AN: 10558

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20148 AN: 67934

Other (OTH) AF: 0.267 AC: 564 AN: 2114

Alfa AF: 0.285 Hom.: 3237

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
PhyloP100		0.048
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: rs12649437; hg19: chr4-155387171;