rs12651106

Variant names:

• chr4-154379907-C-A
• rs12651106
• NM_001358235.2:c.2053-2463G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-154379907-C-A
• chr4-154379907-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358235.2(DCHS2):​c.2053-2463G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,052 control chromosomes in the GnomAD database, including 1,568 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 0.12 (1568 hom., cov: 32)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358235.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	NM_001358235.2	MANE Select	c.2053-2463G>T		intron	N/A	NP_001345164.1	Q6V1P9-1
	DCHS2	NM_001142552.2		c.2053-2463G>T		intron	N/A	NP_001136024.1	Q6V1P9-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	ENST00000357232.10	TSL:1 MANE Select	c.2053-2463G>T		intron	N/A	ENSP00000349768.5	Q6V1P9-1
	DCHS2	ENST00000339452.2	TSL:1	c.2053-2463G>T		intron	N/A	ENSP00000345062.1	Q6V1P9-5
	DCHS2	ENST00000623607.4	TSL:1	n.234-2463G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18651 AN: 151934 Hom.: 1568 Cov.: 32

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0635

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.123 AC: 18667 AN: 152052 Hom.: 1568 Cov.: 32 AF XY: 0.126 AC XY: 9396 AN XY: 74318

African (AFR) AF: 0.0271 AC: 1126 AN: 41522

American (AMR) AF: 0.129 AC: 1962 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0635 AC: 220 AN: 3466

East Asian (EAS) AF: 0.245 AC: 1266 AN: 5162

South Asian (SAS) AF: 0.0995 AC: 480 AN: 4826

European-Finnish (FIN) AF: 0.260 AC: 2746 AN: 10548

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10386 AN: 67968

Other (OTH) AF: 0.105 AC: 221 AN: 2104

Alfa AF: 0.139 Hom.: 4745

Bravo AF: 0.112

Asia WGS AF: 0.176 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12651106; hg19: chr4-155301059; COSMIC: COSV107400793;