NM_144622.3:c.1918G>A

Variant names:

• chr1-155023410-C-T
• rs375988286
• NM_144622.3:c.1918G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144622.3(DCST2):​c.1918G>A​(p.Val640Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,606,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. V640L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: DCST2 NM_144622.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 0 publications found

Genes affected

DCST2 (HGNC:26562): (DC-STAMP domain containing 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2754983).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144622.3. 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
	DCST2	NM_144622.3	MANE Select	c.1918G>A	p.Val640Met	missense	Exon 13 of 15	NP_653223.2	Q5T1A1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCST2	ENST00000368424.4	TSL:1 MANE Select	c.1918G>A	p.Val640Met	missense	Exon 13 of 15	ENSP00000357409.3	Q5T1A1-1
	DCST2	ENST00000368423.5	TSL:2	n.1670G>A		non_coding_transcript_exon	Exon 8 of 10
	DCST2	ENST00000467991.2	TSL:4	n.*162G>A		non_coding_transcript_exon	Exon 3 of 5	ENSP00000437330.2	H0YF62

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000339 AC: 8 AN: 235750 AF XY: 0.0000314

Gnomad AFR exome AF: 0.000139

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000564

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000275 AC: 40 AN: 1454790 Hom.: 0 Cov.: 33 AF XY: 0.0000346 AC XY: 25 AN XY: 723048

African (AFR) AF: 0.0000599 AC: 2 AN: 33382

American (AMR) AF: 0.0000229 AC: 1 AN: 43576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25920

East Asian (EAS) AF: 0.00 AC: 0 AN: 39512

South Asian (SAS) AF: 0.000106 AC: 9 AN: 85084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000244 AC: 27 AN: 1108558

Other (OTH) AF: 0.0000166 AC: 1 AN: 60140

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74340

African (AFR) AF: 0.0000483 AC: 2 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000402 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000495 AC: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.074
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.056
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.90	P
Vest4		0.53
MVP		0.048
MPC		0.14
ClinPred		0.068	T
GERP RS		0.86
Varity_R		0.043
gMVP		0.43
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs375988286; hg19: chr1-154995886;