dbSNP rs1055962026: DOC2B:p.Glu81Gln (chr17-181239-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003585.5(DOC2B):c.241G>C(p.Glu81Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000165 in 1,215,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 9.4e-7 ( 0 hom. )

Consequence

DOC2B
NM_003585.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27245343).

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.241G>C	p.Glu81Gln	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.241G>C	p.Glu81Gln	missense	Exon 1 of 9	ENSP00000482950.1	Q14184
DOC2B	ENST00000697390.1		c.241G>C	p.Glu81Gln	missense	Exon 1 of 10	ENSP00000513293.1	A0A8V8TML1
DOC2B	ENST00000952977.1		c.241G>C	p.Glu81Gln	missense	Exon 1 of 9	ENSP00000623036.1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.39e-7

AC:

AN:

1064798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

502934

show subpopulations

African (AFR)

AF:

0.0000450

AC:

AN:

22226

American (AMR)

AF:

0.00

AC:

AN:

7864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13512

East Asian (EAS)

AF:

0.00

AC:

AN:

25244

South Asian (SAS)

AF:

0.00

AC:

AN:

19544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2824

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

910290

Other (OTH)

AF:

0.00

AC:

AN:

42436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150900

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73692

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41228

American (AMR)

AF:

0.00

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5070

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67574

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

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

0.22

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.13

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.27

MetaSVM

Uncertain

-0.13

PhyloP100

4.7

PrimateAI

Pathogenic

0.94

Sift4G

Benign

0.50

Vest4

0.17

MutPred

0.39

Loss of stability (P = 0.0883)

MVP

0.55

ClinPred

0.91

GERP RS

2.1

PromoterAI

0.11

Neutral

(source)

Varity_R

0.12

gMVP

0.40

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over