Genetic Variant NM_003585.5:c.241G>A (chr17-181239-C-T) – 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>A(p.Glu81Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000133 in 150,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E81Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DOC2B
NM_003585.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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=0.27722883).

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>A	p.Glu81Lys	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>A	p.Glu81Lys	missense	Exon 1 of 9	ENSP00000482950.1	Q14184
DOC2B	ENST00000697390.1		c.241G>A	p.Glu81Lys	missense	Exon 1 of 10	ENSP00000513293.1	A0A8V8TML1
DOC2B	ENST00000952977.1		c.241G>A	p.Glu81Lys	missense	Exon 1 of 9	ENSP00000623036.1

Frequencies

GnomAD3 genomes

AF:

0.0000133

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:

0.000197

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1064798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

502934

African (AFR)

AF:

0.00

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

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150900

Hom.:

Cov.:

AF XY:

0.0000136

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:

0.000197

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: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.28

MetaSVM

Uncertain

-0.27

PhyloP100

4.7

PrimateAI

Pathogenic

0.95

Sift4G

Benign

0.73

Vest4

0.26

MutPred

0.40

Gain of ubiquitination at E81 (P = 0.0025)

MVP

0.68

ClinPred

0.90

GERP RS

2.1

PromoterAI

0.044

Neutral

(source)

Varity_R

0.13

gMVP

0.39

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

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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