Genetic Variant DOC2B:p.Ala63Thr (chr17-181293-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 10/16 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.413

Publications

0 publications found

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]

DOC2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.115935236).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003585.5. 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
	DOC2B	NM_003585.5	MANE Select	c.187G>A	p.Ala63Thr	missense	Exon 1 of 9	NP_003576.2	Q14184

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DOC2B	ENST00000613549.3	TSL:1 MANE Select	c.187G>A	p.Ala63Thr	missense	Exon 1 of 9	ENSP00000482950.1	Q14184
DOC2B	ENST00000697390.1		c.187G>A	p.Ala63Thr	missense	Exon 1 of 10	ENSP00000513293.1	A0A8V8TML1
DOC2B	ENST00000952977.1		c.187G>A	p.Ala63Thr	missense	Exon 1 of 9	ENSP00000623036.1

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149572

Hom.:

Cov.:

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:

AN:

1043526

Hom.:

Cov.:

AF XY:

0.00000203

AC XY:

AN XY:

492660

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21416

American (AMR)

AF:

0.00

AC:

AN:

7146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12438

East Asian (EAS)

AF:

0.00

AC:

AN:

23272

South Asian (SAS)

AF:

0.000104

AC:

AN:

19298

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2716

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

896562

Other (OTH)

AF:

0.00

AC:

AN:

40700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149682

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41154

American (AMR)

AF:

0.00

AC:

AN:

15078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5054

South Asian (SAS)

AF:

0.000208

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67126

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.054

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.46

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.95

PhyloP100

-0.41

PrimateAI

Pathogenic

0.87

Sift4G

Benign

0.49

Vest4

0.055

MutPred

0.30

Gain of glycosylation at A63 (P = 0.0042)

MVP

0.18

ClinPred

0.025

GERP RS

1.9

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.029

gMVP

0.37

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over