chr4-154236938-A-C

Variant names:

• chr4-154236938-A-C
• rs111684589
• NM_001358235.2:c.7714T>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001358235.2(DCHS2):​c.7714T>G​(p.Ser2572Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,614,088 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0068 (8 hom., cov: 32)
  • Exomes 𝑓: 0.011 (102 hom.)
• Consequence: DCHS2 NM_001358235.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.11
• Publications: 8 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]

ENSG00000278981 (HGNC:):

ENSG00000280241 (HGNC:58900):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00484097).
• BP6: Variant 4-154236938-A-C is Benign according to our data. Variant chr4-154236938-A-C is described in ClinVar as Benign. ClinVar VariationId is 3037446.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.7714T>G	p.Ser2572Ala	missense	Exon 20 of 20	NP_001345164.1	Q6V1P9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS2	ENST00000357232.10	TSL:1 MANE Select	c.7714T>G	p.Ser2572Ala	missense	Exon 20 of 20	ENSP00000349768.5	Q6V1P9-1
	DCHS2	ENST00000623607.4	TSL:1	n.6348T>G		non_coding_transcript_exon	Exon 25 of 25
	ENSG00000278981	ENST00000625026.1	TSL:6	n.959A>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00684 AC: 1041 AN: 152226 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00231

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00877

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00692 AC: 1738 AN: 251150 AF XY: 0.00699

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00610

Gnomad ASJ exome AF: 0.00655

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00490

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.00833

GnomAD4 exome AF: 0.0107 AC: 15584 AN: 1461744 Hom.: 102 Cov.: 34 AF XY: 0.0103 AC XY: 7510 AN XY: 727170

African (AFR) AF: 0.00182 AC: 61 AN: 33470

American (AMR) AF: 0.00666 AC: 298 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00677 AC: 177 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000742 AC: 64 AN: 86252

European-Finnish (FIN) AF: 0.00550 AC: 294 AN: 53408

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5764

European-Non Finnish (NFE) AF: 0.0126 AC: 14052 AN: 1111922

Other (OTH) AF: 0.0103 AC: 622 AN: 60388

GnomAD4 genome AF: 0.00683 AC: 1041 AN: 152344 Hom.: 8 Cov.: 32 AF XY: 0.00639 AC XY: 476 AN XY: 74492

African (AFR) AF: 0.00231 AC: 96 AN: 41594

American (AMR) AF: 0.00876 AC: 134 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 714 AN: 68024

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.00923 Hom.: 16

Bravo AF: 0.00757

TwinsUK AF: 0.00998 AC: 37

ALSPAC AF: 0.0104 AC: 40

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.0120 AC: 103

ExAC AF: 0.00675 AC: 820

Asia WGS AF: 0.00173 AC: 7 AN: 3478

EpiCase AF: 0.0107

EpiControl AF: 0.0129

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DCHS2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.88	D
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.69	T
PhyloP100		2.1
PrimateAI	Benign	0.39	T
REVEL	Benign	0.20
MPC		0.18
ClinPred		0.029	T
GERP RS		1.9
gMVP		0.088
Mutation Taster		=96/4	polymorphism

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: rs111684589; hg19: chr4-155158090;