chr13-25415614-C-T

Position:

• chr13-25415614-C-T

Variant summary

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

The ENST00000381655.7(ATP8A2):​c.76+43326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,140 control chromosomes in the GnomAD database, including 5,760 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 0.25 (5760 hom., cov: 32)
• Consequence: ATP8A2 ENST00000381655.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8A2	NM_016529.6	c.76+43326C>T		intron_variant		ENST00000381655.7	NP_057613.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8A2	ENST00000381655.7	c.76+43326C>T		intron_variant		1	NM_016529.6	ENSP00000371070

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37695 AN: 152022 Hom.: 5766 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.248 AC: 37684 AN: 152140 Hom.: 5760 Cov.: 32 AF XY: 0.250 AC XY: 18571 AN XY: 74390

Gnomad4 AFR AF: 0.0988

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.269

Alfa AF: 0.319 Hom.: 10537

Bravo AF: 0.226

Asia WGS AF: 0.120 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.55

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: rs9511790; hg19: chr13-25989752; COSMIC: COSV67714569;