chr1-155018725-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144622.3(DCST2):​c.2141A>G​(p.Lys714Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,594 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: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

DCST2
NM_144622.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0970
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.033054203).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCST2NM_144622.3 linkc.2141A>G p.Lys714Arg missense_variant Exon 15 of 15 ENST00000368424.4 NP_653223.2 Q5T1A1-1
ZBTB7BNM_001256455.2 linkc.*2040T>C downstream_gene_variant ENST00000535420.6 NP_001243384.1 O15156-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCST2ENST00000368424.4 linkc.2141A>G p.Lys714Arg missense_variant Exon 15 of 15 1 NM_144622.3 ENSP00000357409.3 Q5T1A1-1
ZBTB7BENST00000535420.6 linkc.*2040T>C downstream_gene_variant 5 NM_001256455.2 ENSP00000438647.1 O15156-1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152018
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000802
AC:
20
AN:
249230
Hom.:
0
AF XY:
0.0000592
AC XY:
8
AN XY:
135234
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000465
Gnomad NFE exome
AF:
0.000168
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000623
AC:
91
AN:
1461576
Hom.:
0
Cov.:
32
AF XY:
0.0000674
AC XY:
49
AN XY:
727082
show subpopulations
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:
0.000131
Gnomad4 NFE exome
AF:
0.0000710
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152018
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74268
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000319
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000118
AC:
1
ExAC
AF:
0.000132
AC:
16
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 13, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2141A>G (p.K714R) alteration is located in exon 15 (coding exon 15) of the DCST2 gene. This alteration results from a A to G substitution at nucleotide position 2141, causing the lysine (K) at amino acid position 714 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
0.067
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.41
DANN
Benign
0.50
DEOGEN2
Benign
0.018
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.033
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.14
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.20
N
REVEL
Benign
0.0010
Sift
Benign
0.56
T
Sift4G
Benign
0.64
T
Polyphen
0.0
B
Vest4
0.096
MVP
0.13
MPC
0.060
ClinPred
0.037
T
GERP RS
-4.5
Varity_R
0.027
gMVP
0.045

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373443674; hg19: chr1-154991201; API