rs1407130

chr1-160125868-C-T

Variant summary

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

The NM_000702.4(ATP1A2):c.748+615C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,132 control chromosomes in the GnomAD database, including 6,096 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 0.27 (6096 hom., cov: 32)
• Consequence: ATP1A2 NM_000702.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

Genes affected

ATP1A2 (HGNC:800): (ATPase Na+/K+ transporting subunit alpha 2) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, 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 catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 2 subunit. Mutations in this gene result in familial basilar or hemiplegic migraines, and in a rare syndrome known as alternating hemiplegia of childhood. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP1A2	NM_000702.4	c.748+615C>T		intron_variant		ENST00000361216.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1A2	ENST00000361216.8	c.748+615C>T		intron_variant		1	NM_000702.4	P1
ATP1A2	ENST00000392233.7	c.748+615C>T		intron_variant		5
ATP1A2	ENST00000472488.5	n.851+615C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41483 AN: 152012 Hom.: 6096 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.273 AC: 41503 AN: 152132 Hom.: 6096 Cov.: 32 AF XY: 0.274 AC XY: 20399 AN XY: 74372

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.309

Alfa AF: 0.281 Hom.: 1299

Bravo AF: 0.287

Asia WGS AF: 0.358 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.8
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs1407130; hg19: chr1-160095658;