NM_144622.3:c.2315C>G

Variant names:

• chr1-155018551-G-C
• NM_144622.3:c.2315C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144622.3(DCST2):​c.2315C>G​(p.Pro772Arg) 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. 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: -0.518

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05332747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCST2	NM_144622.3	c.2315C>G	p.Pro772Arg	missense_variant	Exon 15 of 15	ENST00000368424.4	NP_653223.2
ZBTB7B	NM_001256455.2	c.*1866G>C		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.2315C>G	p.Pro772Arg	missense_variant	Exon 15 of 15	1	NM_144622.3	ENSP00000357409.3
ZBTB7B	ENST00000535420.6	c.*1866G>C		downstream_gene_variant		5	NM_001256455.2	ENSP00000438647.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2315C>G (p.P772R) alteration is located in exon 15 (coding exon 15) of the DCST2 gene. This alteration results from a C to G substitution at nucleotide position 2315, causing the proline (P) at amino acid position 772 to be replaced by an arginine (R). 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	0.066
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.6
DANN	Benign	0.51
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.20	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.0030
Sift	Benign	0.13	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.24		Loss of glycosylation at P772 (P = 0.004);
MVP		0.014
MPC		0.075
ClinPred		0.15	T
GERP RS		-2.8
Varity_R		0.035
gMVP		0.025

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: chr1-154991027;