rs7983722

Variant names:

• chr13-25871011-G-A
• rs7983722
• NM_016529.6:c.3183+8603G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-25871011-G-A
• chr13-25871011-G-T

Variant summary

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

The NM_016529.6(ATP8A2):​c.3183+8603G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 151,644 control chromosomes in the GnomAD database, including 542 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 0.053 (542 hom., cov: 32)
• Consequence: ATP8A2 NM_016529.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 2 publications found

Genes affected

ATP8A2 (HGNC:13533): (ATPase phospholipid transporting 8A2) The protein encoded by this gene is a member of the P4 ATPase family of proteins, which are thought to be involved in a process called lipid flipping, whereby phospholipids are translocated inwards from the exoplasmic leaflet to the cytosolic leaflet of the cell membrane, which aids in generating and maintaining asymmetry in membrane lipids. This protein is predicted to contain an E1 E2 ATPase, a haloacid dehalogenase-like hydrolase (HAD) domain, and multiple transmembrane domains. Associations between this protein and cell cycle control protein 50A are important for translocation of phosphatidylserine across membranes. Mutations in this gene have been associated with a syndrome (CAMRQ4) characterized by cerebellar ataxia and cognitive disabilities. In addition, a translocation breakpoint within this gene was observed in an individual with neurological dysfunction. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

ATP8A2 Gene-Disease associations (from GenCC):

• cerebellar ataxia, intellectual disability, and dysequilibrium

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 4

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

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 (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016529.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8A2	NM_016529.6	MANE Select	c.3183+8603G>A		intron	N/A	NP_057613.4
	ATP8A2	NM_001411005.1		c.3108+8603G>A		intron	N/A	NP_001397934.1	A0A804HKW9
	ATP8A2	NM_001313741.1		c.2988+8603G>A		intron	N/A	NP_001300670.1	Q9NTI2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8A2	ENST00000381655.7	TSL:1 MANE Select	c.3183+8603G>A		intron	N/A	ENSP00000371070.2	Q9NTI2-4
	ATP8A2	ENST00000281620.11	TSL:1	n.*3001+8603G>A		intron	N/A	ENSP00000281620.7	F8W9B3
	ATP8A2	ENST00000491840.1	TSL:1	n.2054+8603G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0529 AC: 8022 AN: 151544 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0230

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00230

Gnomad OTH AF: 0.0616

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

GnomAD4 genome AF: 0.0532 AC: 8071 AN: 151644 Hom.: 542 Cov.: 32 AF XY: 0.0538 AC XY: 3982 AN XY: 74024

African (AFR) AF: 0.135 AC: 5588 AN: 41328

American (AMR) AF: 0.129 AC: 1973 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3468

East Asian (EAS) AF: 0.0231 AC: 119 AN: 5150

South Asian (SAS) AF: 0.0140 AC: 67 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10400

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00230 AC: 156 AN: 67954

Other (OTH) AF: 0.0615 AC: 129 AN: 2098

Alfa AF: 0.0260 Hom.: 345

Bravo AF: 0.0701

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.033
DANN	Benign	0.73
PhyloP100		-2.9
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: rs7983722; hg19: chr13-26445149; COSMIC: COSV54943210;