rs10494336

Variant names:

• chr1-160137798-G-A
• rs10494336
• NM_000702.4:c.2840+767G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-160137798-G-A
• chr1-160137798-G-C
• chr1-160137798-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000702.4(ATP1A2):​c.2840+767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 145,076 control chromosomes in the GnomAD database, including 1,432 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 0.14 (1432 hom., cov: 31)
• Consequence: ATP1A2 NM_000702.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 9 publications found

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]

ATP1A2 Gene-Disease associations (from GenCC):

• hemiplegic migraine-developmental and epileptic encephalopathy spectrum

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• migraine, familial hemiplegic, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• alternating hemiplegia of childhood 1

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• developmental and epileptic encephalopathy 98

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• alternating hemiplegia of childhood

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial or sporadic hemiplegic migraine

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309097 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1A2	NM_000702.4	c.2840+767G>A		intron_variant	Intron 20 of 22	ENST00000361216.8	NP_000693.1
ATP1A2	XM_047421286.1	c.1949+767G>A		intron_variant	Intron 13 of 15		XP_047277242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1A2	ENST00000361216.8	c.2840+767G>A		intron_variant	Intron 20 of 22	1	NM_000702.4	ENSP00000354490.3

Frequencies

GnomAD3 genomes AF: 0.139 AC: 20151 AN: 144954 Hom.: 1431 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.0919

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.139 AC: 20155 AN: 145076 Hom.: 1432 Cov.: 31 AF XY: 0.139 AC XY: 9829 AN XY: 70582

African (AFR) AF: 0.153 AC: 6183 AN: 40364

American (AMR) AF: 0.102 AC: 1489 AN: 14630

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 400 AN: 3360

East Asian (EAS) AF: 0.180 AC: 787 AN: 4370

South Asian (SAS) AF: 0.281 AC: 1222 AN: 4342

European-Finnish (FIN) AF: 0.0919 AC: 840 AN: 9144

Middle Eastern (MID) AF: 0.136 AC: 39 AN: 286

European-Non Finnish (NFE) AF: 0.132 AC: 8693 AN: 65652

Other (OTH) AF: 0.139 AC: 285 AN: 2044

Alfa AF: 0.123 Hom.: 2459

Bravo AF: 0.130

Asia WGS AF: 0.193 AC: 670 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	1.3
DANN	Benign	0.93
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10494336; hg19: chr1-160107588;