rs72829446

chr17-7648805-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303263.2(ATP1B2):c.-6+2104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 152,056 control chromosomes in the GnomAD database, including 476 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.064 (476 hom., cov: 31)
• Consequence: ATP1B2 NM_001303263.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657

Genes affected

ATP1B2 (HGNC:805): (ATPase Na+/K+ transporting subunit beta 2) The protein encoded by this gene belongs to the family of Na+/K+ and H+/K+ ATPases beta chain proteins, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. The glycoprotein subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes a beta 2 subunit. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1B2	NM_001303263.2	c.-6+2104C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1B2	ENST00000577026.5	c.-6+2104C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0645 AC: 9797 AN: 151938 Hom.: 476 Cov.: 31

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0678

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0644 AC: 9792 AN: 152056 Hom.: 476 Cov.: 31 AF XY: 0.0597 AC XY: 4438 AN XY: 74316

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0671

Alfa AF: 0.0761 Hom.: 58

Bravo AF: 0.0654

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.6
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72829446; hg19: chr17-7552123;