chr17-181293-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003585.5(DOC2B):​c.187G>A​(p.Ala63Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,193,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

DOC2B
NM_003585.5 missense

Scores

2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.413
Variant links:
Genes affected
DOC2B (HGNC:2986): (double C2 domain beta) There are at least two protein isoforms of the Double C2 protein, namely alpha (DOC2A) and beta (DOC2B), which contain two C2-like domains. DOC2A and DOC2B are encoded by different genes; these genes are at times confused with the unrelated DAB2 gene which was initially named DOC-2. DOC2B is expressed ubiquitously and is suggested to be involved in Ca(2+)-dependent intracellular vesicle trafficking in various types of cells. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

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=0.115935236).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DOC2BNM_003585.5 linkc.187G>A p.Ala63Thr missense_variant Exon 1 of 9 ENST00000613549.3 NP_003576.2 Q14184

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DOC2BENST00000613549.3 linkc.187G>A p.Ala63Thr missense_variant Exon 1 of 9 1 NM_003585.5 ENSP00000482950.1 Q14184
DOC2BENST00000697390.1 linkc.187G>A p.Ala63Thr missense_variant Exon 1 of 10 ENSP00000513293.1 A0A8V8TML1
DOC2BENST00000609727.1 linkn.-123G>A upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000669
AC:
1
AN:
149572
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:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000192
AC:
2
AN:
1043526
Hom.:
0
Cov.:
31
AF XY:
0.00000203
AC XY:
1
AN XY:
492660
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:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000668
AC:
1
AN:
149682
Hom.:
0
Cov.:
32
AF XY:
0.0000137
AC XY:
1
AN XY:
73110
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:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.187G>A (p.A63T) alteration is located in exon 1 (coding exon 1) of the DOC2B gene. This alteration results from a G to A substitution at nucleotide position 187, causing the alanine (A) at amino acid position 63 to be replaced by a threonine (T). 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
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
10
DANN
Benign
0.89
DEOGEN2
Benign
0.054
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.46
T
M_CAP
Pathogenic
0.72
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.95
T
PrimateAI
Pathogenic
0.87
D
Sift4G
Benign
0.49
T
Vest4
0.055
MutPred
0.30
Gain of glycosylation at A63 (P = 0.0042);
MVP
0.18
ClinPred
0.025
T
GERP RS
1.9
Varity_R
0.029
gMVP
0.37

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

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

Other links and lift over

dbSNP: rs2040439962; hg19: chr17-31084; API