ENST00000623607.4:n.457T>C

Variant names:

• chr4-154373924-A-G
• rs11721758
• ENST00000623607.4:n.457T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The ENST00000623607.4(DCHS2):​n.457T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,597,486 control chromosomes in the GnomAD database, including 152,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.37 (11083 hom., cov: 28)
  • Exomes 𝑓: 0.44 (141850 hom.)
• Consequence: DCHS2 ENST00000623607.4 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0600
• Publications: 32 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]

ENSG00000249200 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.029).
• BP6: Variant 4-154373924-A-G is Benign according to our data. Variant chr4-154373924-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060662.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000623607.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	NM_001358235.2	MANE Select	c.2244+3329T>C		intron	N/A	NP_001345164.1
	DCHS2	NM_001142552.2		c.2244+3329T>C		intron	N/A	NP_001136024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	ENST00000623607.4	TSL:1	n.457T>C		non_coding_transcript_exon	Exon 4 of 25
	DCHS2	ENST00000357232.10	TSL:1 MANE Select	c.2244+3329T>C		intron	N/A	ENSP00000349768.5
	DCHS2	ENST00000339452.2	TSL:1	c.2244+3329T>C		intron	N/A	ENSP00000345062.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55142 AN: 149580 Hom.: 11084 Cov.: 28

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.385

GnomAD2 exomes AF: 0.403 AC: 98214 AN: 243854 AF XY: 0.410

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.405

Gnomad EAS exome AF: 0.372

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.444

Gnomad OTH exome AF: 0.405

GnomAD4 exome AF: 0.438 AC: 634801 AN: 1447792 Hom.: 141850 Cov.: 31 AF XY: 0.439 AC XY: 316475 AN XY: 720354

African (AFR) AF: 0.171 AC: 5655 AN: 33042

American (AMR) AF: 0.360 AC: 15716 AN: 43626

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 10494 AN: 25794

East Asian (EAS) AF: 0.370 AC: 14459 AN: 39068

South Asian (SAS) AF: 0.435 AC: 36826 AN: 84626

European-Finnish (FIN) AF: 0.410 AC: 21745 AN: 53034

Middle Eastern (MID) AF: 0.443 AC: 2529 AN: 5704

European-Non Finnish (NFE) AF: 0.455 AC: 502073 AN: 1103118

Other (OTH) AF: 0.423 AC: 25304 AN: 59780

GnomAD4 genome AF: 0.368 AC: 55152 AN: 149694 Hom.: 11083 Cov.: 28 AF XY: 0.371 AC XY: 27015 AN XY: 72842

African (AFR) AF: 0.189 AC: 7669 AN: 40602

American (AMR) AF: 0.393 AC: 5862 AN: 14934

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1421 AN: 3458

East Asian (EAS) AF: 0.378 AC: 1901 AN: 5024

South Asian (SAS) AF: 0.452 AC: 2143 AN: 4738

European-Finnish (FIN) AF: 0.423 AC: 4253 AN: 10048

Middle Eastern (MID) AF: 0.396 AC: 114 AN: 288

European-Non Finnish (NFE) AF: 0.454 AC: 30668 AN: 67622

Other (OTH) AF: 0.382 AC: 792 AN: 2076

Alfa AF: 0.425 Hom.: 63537

Bravo AF: 0.353

Asia WGS AF: 0.386 AC: 1344 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DCHS2-related disorder Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.1
DANN	Benign	0.84
PhyloP100		0.060
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs11721758; hg19: chr4-155295076; COSMIC: COSV59721405;