1-155023386-G-C

Position:

• chr1-155023386-G-C

Variant summary

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

The NM_144622.3(DCST2):​c.1942C>G​(p.Gln648Glu) 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. 15/21 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: 2.22

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09369984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCST2	NM_144622.3	c.1942C>G	p.Gln648Glu	missense_variant	13/15	ENST00000368424.4	NP_653223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCST2	ENST00000368424.4	c.1942C>G	p.Gln648Glu	missense_variant	13/15	1	NM_144622.3	ENSP00000357409.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jul 06, 2021

The c.1942C>G (p.Q648E) alteration is located in exon 13 (coding exon 13) of the DCST2 gene. This alteration results from a C to G substitution at nucleotide position 1942, causing the glutamine (Q) at amino acid position 648 to be replaced by a glutamic acid (E). 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	0.091
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.79
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.046
Sift	Benign	0.34	T
Sift4G	Benign	0.41	T
Polyphen		0.0040	B
Vest4		0.25
MutPred		0.21		Gain of disorder (P = 0.1149);
MVP		0.12
MPC		0.081
ClinPred		0.14	T
GERP RS		3.2
Varity_R		0.047
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs1659807211; hg19: chr1-154995862;