4-154236809-C-A

Variant names:

• chr4-154236809-C-A
• rs61741015
• NM_001358235.2:c.7843G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001358235.2(DCHS2):​c.7843G>T​(p.Gly2615Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2615S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCHS2 NM_001358235.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.76
• Publications: 2 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

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.7843G>T	p.Gly2615Cys	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.7843G>T	p.Gly2615Cys	missense	Exon 20 of 20	ENSP00000349768.5	Q6V1P9-1
	DCHS2	ENST00000623607.4	TSL:1	n.6477G>T		non_coding_transcript_exon	Exon 25 of 25
	ENSG00000278981	ENST00000625026.1	TSL:6	n.830C>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.41	D
PhyloP100		4.8
PrimateAI	Benign	0.44	T
REVEL	Uncertain	0.49
MPC		0.44
ClinPred		1.0	D
GERP RS		6.0
gMVP		0.54
Mutation Taster		=72/28	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: rs61741015; hg19: chr4-155157961;