17-7654054-T-A

Position:

chr17-7654054-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001678.5(ATP1B2):c.349T>A(p.Tyr117Asn) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATP1B2
NM_001678.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

Variant links:

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]

ATP1B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1B2	NM_001678.5 linkuse as main transcript	c.349T>A	p.Tyr117Asn	missense_variant, splice_region_variant	4/7	ENST00000250111.9	NP_001669.3	P14415
ATP1B2	NM_001303263.2 linkuse as main transcript	c.103T>A	p.Tyr35Asn	missense_variant, splice_region_variant	3/6		NP_001290192.1	P14415

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1B2	ENST00000250111.9 linkuse as main transcript	c.349T>A	p.Tyr117Asn	missense_variant, splice_region_variant	4/7	1	NM_001678.5	ENSP00000250111.4		P14415
ATP1B2	ENST00000577026.5 linkuse as main transcript	c.103T>A	p.Tyr35Asn	missense_variant, splice_region_variant	3/6	4		ENSP00000459145.1		I3L1V9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150940

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000656

AC:

AN:

1402532

Hom.:

Cov.:

AF XY:

0.0000572

AC XY:

AN XY:

699404

show subpopulations

Gnomad4 AFR exome

AF:

0.0000942

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.000124

Gnomad4 EAS exome

AF:

0.0000831

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.0000973

Gnomad4 NFE exome

AF:

0.0000656

Gnomad4 OTH exome

AF:

0.0000701

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000662

AC:

AN:

151070

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73848

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

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

Mar 14, 2024

The c.349T>A (p.Y117N) alteration is located in exon 4 (coding exon 4) of the ATP1B2 gene. This alteration results from a T to A substitution at nucleotide position 349, causing the tyrosine (Y) at amino acid position 117 to be replaced by an asparagine (N). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.57

.;D

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Uncertain

-0.090

MutationAssessor

Pathogenic

3.8

.;H

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-8.7

.;D

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.95

MutPred

0.90

.;Gain of disorder (P = 0.0098);

MVP

0.80

MPC

1.3

ClinPred

1.0

GERP RS

4.7

Varity_R

0.97

gMVP

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over