17-7655813-A-C

Position:

• chr17-7655813-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001678.5(ATP1B2):​c.791A>C​(p.Asn264Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATP1B2 NM_001678.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1B2	NM_001678.5	c.791A>C	p.Asn264Thr	missense_variant	7/7	ENST00000250111.9	NP_001669.3
ATP1B2	NM_001303263.2	c.545A>C	p.Asn182Thr	missense_variant	6/6		NP_001290192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1B2	ENST00000250111.9	c.791A>C	p.Asn264Thr	missense_variant	7/7	1	NM_001678.5	ENSP00000250111.4
ATP1B2	ENST00000577113.1	c.434A>C	p.Asn145Thr	missense_variant	6/6	3		ENSP00000460499.1
ATP1B2	ENST00000577026.5	c.*45A>C		downstream_gene_variant		4		ENSP00000459145.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.791A>C (p.N264T) alteration is located in exon 7 (coding exon 7) of the ATP1B2 gene. This alteration results from a A to C substitution at nucleotide position 791, causing the asparagine (N) at amino acid position 264 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.31
Sift	Benign	0.065	T
Sift4G	Benign	0.50	T
Polyphen		1.0	D
Vest4		0.47
MutPred		0.45		Loss of catalytic residue at N264 (P = 0.0863);
MVP		0.52
MPC		0.73
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.43
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7559131;