1-155024592-G-A

Position:

• chr1-155024592-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144622.3(DCST2):​c.1622C>T​(p.Ser541Phe) 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. 12/21 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)
• Consequence: DCST2 NM_144622.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07

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]

DCST2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34564534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCST2	NM_144622.3	c.1622C>T	p.Ser541Phe	missense_variant	11/15	ENST00000368424.4	NP_653223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCST2	ENST00000368424.4	c.1622C>T	p.Ser541Phe	missense_variant	11/15	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.1622C>T (p.S541F) alteration is located in exon 11 (coding exon 11) of the DCST2 gene. This alteration results from a C to T substitution at nucleotide position 1622, causing the serine (S) at amino acid position 541 to be replaced by a phenylalanine (F). 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	0.27
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.086
Sift	Benign	0.048	D
Sift4G	Uncertain	0.018	D
Polyphen		0.77	P
Vest4		0.51
MutPred		0.59		Loss of disorder (P = 0.0139);
MVP		0.36
MPC		0.26
ClinPred		0.77	D
GERP RS		3.2
Varity_R		0.087
gMVP		0.27

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-154997068;