rs7997094

chr13-25952174-C-T

Variant summary

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

The NM_016529.6(ATP8A2):c.3184-9401C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,098 control chromosomes in the GnomAD database, including 2,117 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 0.10 (2117 hom., cov: 32)
• Consequence: ATP8A2 NM_016529.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8A2	NM_016529.6	c.3184-9401C>T		intron_variant		ENST00000381655.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8A2	ENST00000381655.7	c.3184-9401C>T		intron_variant		1	NM_016529.6

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15931 AN: 151980 Hom.: 2102 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.00810

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.00472

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.105 AC: 15970 AN: 152098 Hom.: 2117 Cov.: 32 AF XY: 0.102 AC XY: 7597 AN XY: 74342

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.00831

Gnomad4 SAS AF: 0.0652

Gnomad4 FIN AF: 0.00472

Gnomad4 NFE AF: 0.0265

Gnomad4 OTH AF: 0.0800

Alfa AF: 0.0915 Hom.: 337

Bravo AF: 0.118

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.20
Dann	Benign	0.52

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: rs7997094; hg19: chr13-26526312;