17-7654243-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001678.5(ATP1B2):c.538A>C(p.Ile180Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,714 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 1 hom. )
Consequence
ATP1B2
NM_001678.5 missense
NM_001678.5 missense
Scores
6
8
Clinical Significance
Conservation
PhyloP100: 1.93
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.39417946).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP1B2 | NM_001678.5 | c.538A>C | p.Ile180Leu | missense_variant | 4/7 | ENST00000250111.9 | |
ATP1B2 | NM_001303263.2 | c.292A>C | p.Ile98Leu | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP1B2 | ENST00000250111.9 | c.538A>C | p.Ile180Leu | missense_variant | 4/7 | 1 | NM_001678.5 | P1 | |
ATP1B2 | ENST00000577113.1 | c.136A>C | p.Ile46Leu | missense_variant | 1/6 | 3 | |||
ATP1B2 | ENST00000577026.5 | c.292A>C | p.Ile98Leu | missense_variant | 3/6 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461714Hom.: 1 Cov.: 37 AF XY: 0.0000138 AC XY: 10AN XY: 727132
GnomAD4 exome
AF:
AC:
14
AN:
1461714
Hom.:
Cov.:
37
AF XY:
AC XY:
10
AN XY:
727132
Gnomad4 AFR exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 21, 2021 | The c.538A>C (p.I180L) alteration is located in exon 4 (coding exon 4) of the ATP1B2 gene. This alteration results from a A to C substitution at nucleotide position 538, causing the isoleucine (I) at amino acid position 180 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T
Polyphen
0.96
.;D
Vest4
0.30
MutPred
0.63
.;Loss of methylation at K181 (P = 0.0806);
MVP
MPC
0.38
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at