rs912514

Variant names:

• chr13-25970231-C-T
• rs912514
• NM_016529.6:c.3377+1552C>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.3377+1552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,058 control chromosomes in the GnomAD database, including 7,891 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 0.31 (7891 hom., cov: 32)
• Consequence: ATP8A2 NM_016529.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 8 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 syndrome 4

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• cerebellar ataxia, intellectual disability, and dysequilibrium

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8A2	NM_016529.6	c.3377+1552C>T		intron_variant	Intron 35 of 36	ENST00000381655.7	NP_057613.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8A2	ENST00000381655.7	c.3377+1552C>T		intron_variant	Intron 35 of 36	1	NM_016529.6	ENSP00000371070.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47732 AN: 151940 Hom.: 7877 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.314 AC: 47781 AN: 152058 Hom.: 7891 Cov.: 32 AF XY: 0.314 AC XY: 23343 AN XY: 74314

African (AFR) AF: 0.235 AC: 9761 AN: 41498

American (AMR) AF: 0.303 AC: 4638 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3472

East Asian (EAS) AF: 0.168 AC: 870 AN: 5178

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4808

European-Finnish (FIN) AF: 0.367 AC: 3867 AN: 10532

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24340 AN: 67968

Other (OTH) AF: 0.314 AC: 663 AN: 2114

Alfa AF: 0.348 Hom.: 38343

Bravo AF: 0.302

Asia WGS AF: 0.287 AC: 999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.72
PhyloP100		0.061
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: rs912514; hg19: chr13-26544369;