NM_144622.3:c.1765G>T

Variant names:

• chr1-155023937-C-A
• rs1659825607
• NM_144622.3:c.1765G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144622.3(DCST2):​c.1765G>T​(p.Val589Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: DCST2 NM_144622.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.44
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106030464).

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.1765G>T	p.Val589Phe	missense	Exon 12 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.1765G>T	p.Val589Phe	missense	Exon 12 of 15	ENSP00000357409.3	Q5T1A1-1
	DCST2	ENST00000368423.5	TSL:2	n.1517G>T		non_coding_transcript_exon	Exon 7 of 10
	DCST2	ENST00000467991.2	TSL:4	n.*9G>T		non_coding_transcript_exon	Exon 2 of 5	ENSP00000437330.2	H0YF62

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461074 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726786

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.1
DANN	Benign	0.95
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-1.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.054
Sift	Uncertain	0.018	D
Sift4G	Benign	0.073	T
Polyphen		0.61	P
Vest4		0.24
MutPred		0.37		Loss of catalytic residue at V589 (P = 0.1643)
MVP		0.18
MPC		0.14
ClinPred		0.17	T
GERP RS		-8.2
Varity_R		0.071
gMVP		0.45
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1659825607; hg19: chr1-154996413;