1-155018611-G-A

Variant names:

• chr1-155018611-G-A
• rs1434881158
• NM_144622.3:c.2255C>T

Variant summary

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

The NM_144622.3(DCST2):​c.2255C>T​(p.Ala752Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: DCST2 NM_144622.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.870

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]

ZBTB7B (HGNC:18668): (zinc finger and BTB domain containing 7B) This gene encodes a zinc finger-containing transcription factor that acts as a key regulator of lineage commitment of immature T-cell precursors. It is necessary and sufficient for commitment of CD4 lineage, while its absence causes CD8 commitment. It also functions as a transcriptional repressor of type I collagen genes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

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=0.10847834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCST2	NM_144622.3	c.2255C>T	p.Ala752Val	missense_variant	Exon 15 of 15	ENST00000368424.4	NP_653223.2
ZBTB7B	NM_001256455.2	c.*1926G>A		downstream_gene_variant		ENST00000535420.6	NP_001243384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCST2	ENST00000368424.4	c.2255C>T	p.Ala752Val	missense_variant	Exon 15 of 15	1	NM_144622.3	ENSP00000357409.3
ZBTB7B	ENST00000535420.6	c.*1926G>A		downstream_gene_variant		5	NM_001256455.2	ENSP00000438647.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461696 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2255C>T (p.A752V) alteration is located in exon 15 (coding exon 15) of the DCST2 gene. This alteration results from a C to T substitution at nucleotide position 2255, causing the alanine (A) at amino acid position 752 to be replaced by a valine (V). 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	0.086
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.087
Sift	Benign	0.57	T
Sift4G	Benign	0.25	T
Polyphen		0.98	D
Vest4		0.14
MutPred		0.092		Loss of relative solvent accessibility (P = 0.0186);
MVP		0.10
MPC		0.071
ClinPred		0.22	T
GERP RS		1.1
Varity_R		0.056
gMVP		0.028

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: rs1434881158; hg19: chr1-154991087; COSMIC: COSV52691606; COSMIC: COSV52691606;