8-20197420-CGATGCGGGG-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_001693.4(ATP6V1B2):c.18_26del(p.Met6_Gly8del) variant causes a 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 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.02

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 2658457.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V1B2	NM_001693.4	c.18_26del	p.Met6_Gly8del	inframe_deletion	1/14	ENST00000276390.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V1B2	ENST00000276390.7	c.18_26del	p.Met6_Gly8del	inframe_deletion	1/14	1	NM_001693.4	P1

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152152 Hom.: 1 Cov.: 33

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

GnomAD3 exomes AF: 0.00104 AC: 175 AN: 168542 Hom.: 4 AF XY: 0.00153 AC XY: 143 AN XY: 93664

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 SAS exome AF: 0.00686

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.: 8 AF XY: 0.000802 AC XY: 554 AN XY: 690804

Gnomad4 AFR exome AF: 0.0000347

Gnomad4 AMR exome AF: 0.0000277

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000309

Gnomad4 SAS exome AF: 0.00809

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000427

Gnomad4 OTH exome AF: 0.000616

GnomAD4 genome AF: 0.000335 AC: 51 AN: 152270 Hom.: 1 Cov.: 33 AF XY: 0.000510 AC XY: 38 AN XY: 74460

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000130 Hom.: 1

Bravo AF: 0.0000907

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ATP6V1B2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs548097755; hg19: chr8-20054931;