NM_001358235.2:c.8929A>C

Variant names:

• chr4-154235723-T-G
• rs61746101
• NM_001358235.2:c.8929A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001358235.2(DCHS2):​c.8929A>C​(p.Asn2977His) variant causes a missense change. The variant allele was found at a frequency of 0.0076 in 1,613,842 control chromosomes in the GnomAD database, including 691 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.039 (370 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (321 hom.)
• Consequence: DCHS2 NM_001358235.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.21
• Publications: 6 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]

ENSG00000280241 (HGNC:58900):

LOC101927947 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018635988).
• BP6: Variant 4-154235723-T-G is Benign according to our data. Variant chr4-154235723-T-G is described in ClinVar as Benign. ClinVar VariationId is 3055622.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 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.8929A>C	p.Asn2977His	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.8929A>C	p.Asn2977His	missense	Exon 20 of 20	ENSP00000349768.5	Q6V1P9-1
	DCHS2	ENST00000623607.4	TSL:1	n.7563A>C		non_coding_transcript_exon	Exon 25 of 25
	ENSG00000280241	ENST00000623325.1	TSL:5	n.98+28670T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0394 AC: 5996 AN: 152082 Hom.: 371 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.0417

GnomAD2 exomes AF: 0.0106 AC: 2668 AN: 250840 AF XY: 0.00801

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.00726

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000900

Gnomad OTH exome AF: 0.00605

GnomAD4 exome AF: 0.00428 AC: 6254 AN: 1461642 Hom.: 321 Cov.: 34 AF XY: 0.00382 AC XY: 2776 AN XY: 727136

African (AFR) AF: 0.135 AC: 4513 AN: 33472

American (AMR) AF: 0.00778 AC: 348 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00394 AC: 103 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39670

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53406

Middle Eastern (MID) AF: 0.0134 AC: 77 AN: 5762

European-Non Finnish (NFE) AF: 0.000559 AC: 622 AN: 1111846

Other (OTH) AF: 0.00924 AC: 558 AN: 60384

GnomAD4 genome AF: 0.0394 AC: 6004 AN: 152200 Hom.: 370 Cov.: 32 AF XY: 0.0371 AC XY: 2764 AN XY: 74418

African (AFR) AF: 0.134 AC: 5579 AN: 41522

American (AMR) AF: 0.0156 AC: 239 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

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

South Asian (SAS) AF: 0.000624 AC: 3 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.000971 AC: 66 AN: 68004

Other (OTH) AF: 0.0417 AC: 88 AN: 2110

Alfa AF: 0.0127 Hom.: 225

Bravo AF: 0.0450

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.129 AC: 567

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.0131 AC: 1589

Asia WGS AF: 0.00693 AC: 24 AN: 3476

EpiCase AF: 0.00125

EpiControl AF: 0.00154

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	0.21
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.2
PrimateAI	Uncertain	0.50	T
REVEL	Uncertain	0.31
MPC		0.43
ClinPred		0.012	T
GERP RS		5.7
gMVP		0.19
Mutation Taster		=88/12	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: rs61746101; hg19: chr4-155156875;