NM_001303263.2:c.-6+2104C>T

Variant names:

• chr17-7648805-C-T
• rs72829446
• NM_001303263.2:c.-6+2104C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303263.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B2	NM_001303263.2		c.-6+2104C>T		intron	N/A	NP_001290192.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B2	ENST00000577026.5	TSL:4	c.-6+2104C>T		intron	N/A	ENSP00000459145.1

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

African (AFR) AF: 0.0192 AC: 798 AN: 41494

American (AMR) AF: 0.0566 AC: 864 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.00767 AC: 37 AN: 4826

European-Finnish (FIN) AF: 0.0450 AC: 476 AN: 10576

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7016 AN: 67976

Other (OTH) AF: 0.0671 AC: 141 AN: 2102

Alfa AF: 0.0853 Hom.: 922

Bravo AF: 0.0654

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.37
PhyloP100		0.66

Splicing

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

Other links and lift over

dbSNP: rs72829446; hg19: chr17-7552123;