Genetic Variant NM_001693.4:c.18_26delGCGGGGGAT (chr8-20197420-CGATGCGGGG-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_001693.4(ATP6V1B2):c.18_26delGCGGGGGAT(p.Met6_Gly8del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000516 in 1,543,200 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00054 ( 8 hom. )

Consequence

ATP6V1B2
NM_001693.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.02

Publications

0 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 -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001693.4.

BP6

Variant 8-20197420-CGATGCGGGG-C is Benign according to our data. Variant chr8-20197420-CGATGCGGGG-C is described in ClinVar as Benign. ClinVar VariationId is 2658457.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR,AD gene

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.18_26delGCGGGGGAT	p.Met6_Gly8del	disruptive_inframe_deletion	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.18_26delGCGGGGGAT	p.Met6_Gly8del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000276390.2	P21281
ATP6V1B2	ENST00000891263.1		c.18_26delGCGGGGGAT	p.Met6_Gly8del	disruptive_inframe_deletion	Exon 1 of 15	ENSP00000561322.1
ATP6V1B2	ENST00000958718.1		c.18_26delGCGGGGGAT	p.Met6_Gly8del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000628777.1

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152152

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:

0.00890

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00104

AC:

175

AN:

168542

AF XY:

0.00153

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000950

Gnomad OTH exome

AF:

0.000259

GnomAD4 exome

AF:

0.000536

AC:

745

AN:

1390930

Hom.:

AF XY:

0.000802

AC XY:

554

AN XY:

690804

show subpopulations

African (AFR)

AF:

0.0000347

AC:

AN:

28820

American (AMR)

AF:

0.0000277

AC:

AN:

36038

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23990

East Asian (EAS)

AF:

0.0000309

AC:

AN:

32356

South Asian (SAS)

AF:

0.00809

AC:

647

AN:

79982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50294

Middle Eastern (MID)

AF:

0.00313

AC:

AN:

4476

European-Non Finnish (NFE)

AF:

0.0000427

AC:

AN:

1078178

Other (OTH)

AF:

0.000616

AC:

AN:

56796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.403

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000335

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00891

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68004

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000130

Hom.:

Bravo

AF:

0.0000907

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.0

Mutation Taster

=150/50

polymorphism

(source)

Splicing

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