1-155024554-G-T

Variant names:

• chr1-155024554-G-T
• NM_144622.3:c.1660C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144622.3(DCST2):​c.1660C>A​(p.Leu554Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCST2 NM_144622.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.746

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1505008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCST2	NM_144622.3	c.1660C>A	p.Leu554Met	missense_variant	Exon 11 of 15	ENST00000368424.4	NP_653223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCST2	ENST00000368424.4	c.1660C>A	p.Leu554Met	missense_variant	Exon 11 of 15	1	NM_144622.3	ENSP00000357409.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1660C>A (p.L554M) alteration is located in exon 11 (coding exon 11) of the DCST2 gene. This alteration results from a C to A substitution at nucleotide position 1660, causing the leucine (L) at amino acid position 554 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.046
Sift	Benign	0.090	T
Sift4G	Benign	0.12	T
Polyphen		0.93	P
Vest4		0.25
MutPred		0.42		Gain of MoRF binding (P = 0.0789);
MVP		0.17
MPC		0.088
ClinPred		0.15	T
GERP RS		2.1
Varity_R		0.059
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-154997030;