chr1-155018551-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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: -0.518
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144622.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCST2	NM_144622.3	MANE Select	c.2315C>G	p.Pro772Arg	missense	Exon 15 of 15	NP_653223.2	Q5T1A1-1
	ZBTB7B	NM_001256455.2	MANE Select	c.*1866G>C		downstream_gene	N/A	NP_001243384.1	O15156-1
	ZBTB7B	NM_001252406.3		c.*1866G>C		downstream_gene	N/A	NP_001239335.1	O15156-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCST2	ENST00000368424.4	TSL:1 MANE Select	c.2315C>G	p.Pro772Arg	missense	Exon 15 of 15	ENSP00000357409.3	Q5T1A1-1
	DCST2	ENST00000368423.5	TSL:2	n.2067C>G		non_coding_transcript_exon	Exon 10 of 10
	DCST2	ENST00000485982.5	TSL:2	n.*463C>G		non_coding_transcript_exon	Exon 16 of 16	ENSP00000436964.1	Q5T1A1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.52
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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr1-154991027;