NM_001358235.2:c.2052+21209A>G

Variant names:

• chr4-154468095-T-C
• rs17031671
• NM_001358235.2:c.2052+21209A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001358235.2(DCHS2):​c.2052+21209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 152,218 control chromosomes in the GnomAD database, including 81 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 0.019 (81 hom., cov: 32)
• Consequence: DCHS2 NM_001358235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 7 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCHS2	NM_001358235.2	c.2052+21209A>G		intron_variant	Intron 1 of 19	ENST00000357232.10	NP_001345164.1
DCHS2	NM_001142552.2	c.2052+21209A>G		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+21209A>G		intron_variant	Intron 1 of 19	1	NM_001358235.2	ENSP00000349768.5
DCHS2	ENST00000339452.2	c.2052+21209A>G		intron_variant	Intron 1 of 7	1		ENSP00000345062.1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2895 AN: 152100 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0190 AC: 2897 AN: 152218 Hom.: 81 Cov.: 32 AF XY: 0.0181 AC XY: 1349 AN XY: 74430

African (AFR) AF: 0.0645 AC: 2678 AN: 41532

American (AMR) AF: 0.0104 AC: 159 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 67980

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.00965 Hom.: 72

Bravo AF: 0.0217

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		-0.026
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: rs17031671; hg19: chr4-155389247;