8-20197449-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001693.4(ATP6V1B2):c.43C>G(p.Pro15Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,539,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P15S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ATP6V1B2
NM_001693.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.714

Publications

1 publications found

Variant links:

Genes affected

ATP6V1B2 (HGNC:854): (ATPase H+ transporting V1 subunit B2) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A, three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site. The protein encoded by this gene is one of two V1 domain B subunit isoforms and is the only B isoform highly expressed in osteoclasts. [provided by RefSeq, Jul 2008]

ATP6V1B2 Gene-Disease associations (from GenCC):

autosomal dominant deafness - onychodystrophy syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
developmental and epileptic encephalopathy 93
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
Zimmermann-Laband syndrome 2
Inheritance: AD Classification: STRONG Submitted by: G2P
DOORS syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Zimmermann-Laband syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ATP6V1B2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04849106).

BP6

Variant 8-20197449-C-G is Benign according to our data. Variant chr8-20197449-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2594749.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001693.4. 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
	ATP6V1B2	NM_001693.4	MANE Select	c.43C>G	p.Pro15Ala	missense	Exon 1 of 14	NP_001684.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP6V1B2	ENST00000276390.7	TSL:1 MANE Select	c.43C>G	p.Pro15Ala	missense	Exon 1 of 14	ENSP00000276390.2	P21281
ATP6V1B2	ENST00000519667.1	TSL:1	c.10C>G	p.Pro4Ala	missense	Exon 1 of 6	ENSP00000430682.1	H0YC04
ATP6V1B2	ENST00000891263.1		c.43C>G	p.Pro15Ala	missense	Exon 1 of 15	ENSP00000561322.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

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:

0.000193

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

GnomAD2 exomes

AF:

0.000115

AC:

AN:

164556

AF XY:

0.000120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000416

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000440

AC:

AN:

1387190

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

688832

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28702

American (AMR)

AF:

0.00

AC:

AN:

35158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23542

East Asian (EAS)

AF:

0.0000306

AC:

AN:

32652

South Asian (SAS)

AF:

0.000454

AC:

AN:

79308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50210

Middle Eastern (MID)

AF:

0.000197

AC:

AN:

5068

European-Non Finnish (NFE)

AF:

0.0000214

AC:

AN:

1075892

Other (OTH)

AF:

0.00

AC:

AN:

56658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2086

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

Age Distribution

Genome 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

Alfa

AF:

0.0000274

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000997

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.22

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.099

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.84

M_CAP

Benign

0.059

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.71

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.16

REVEL

Benign

0.23

Sift

Benign

0.098

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.43

MutPred

0.28

Loss of glycosylation at P15 (P = 0.0546)

MVP

0.59

MPC

0.013

ClinPred

0.042

GERP RS

2.9

PromoterAI

0.076

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.48

Mutation Taster

=93/7

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over