NM_001358235.2:c.2053-48797T>A

Variant names:

• chr4-154426241-A-T
• rs1466662
• NM_001358235.2:c.2053-48797T>A

Variant summary

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

The NM_001358235.2(DCHS2):​c.2053-48797T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,084 control chromosomes in the GnomAD database, including 7,908 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 0.29 (7908 hom., cov: 33)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 14 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCHS2	NM_001358235.2	c.2053-48797T>A		intron_variant	Intron 1 of 19	ENST00000357232.10	NP_001345164.1
DCHS2	NM_001142552.2	c.2053-48797T>A		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.2053-48797T>A		intron_variant	Intron 1 of 19	1	NM_001358235.2	ENSP00000349768.5
DCHS2	ENST00000339452.2	c.2053-48797T>A		intron_variant	Intron 1 of 7	1		ENSP00000345062.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43840 AN: 151966 Hom.: 7907 Cov.: 33

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.288 AC: 43858 AN: 152084 Hom.: 7908 Cov.: 33 AF XY: 0.297 AC XY: 22041 AN XY: 74314

African (AFR) AF: 0.0842 AC: 3496 AN: 41512

American (AMR) AF: 0.337 AC: 5152 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3495 AN: 5160

South Asian (SAS) AF: 0.349 AC: 1682 AN: 4822

European-Finnish (FIN) AF: 0.435 AC: 4584 AN: 10544

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23251 AN: 67992

Other (OTH) AF: 0.269 AC: 568 AN: 2112

Alfa AF: 0.349 Hom.: 5529

Bravo AF: 0.278

Asia WGS AF: 0.464 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.71
PhyloP100		0.28
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: rs1466662; hg19: chr4-155347393;