rs11616429

Variant names:

• chr13-25978468-G-T
• rs11616429
• NM_016529.6:c.3377+9789G>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+9789G>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 152,180 control chromosomes in the GnomAD database, including 893 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 (893 hom., cov: 32)
• Consequence: ATP8A2 NM_016529.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8A2	NM_016529.6	c.3377+9789G>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+9789G>T		intron_variant	Intron 35 of 36	1	NM_016529.6	ENSP00000371070.2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15926 AN: 152062 Hom.: 891 Cov.: 32

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.105 AC: 15932 AN: 152180 Hom.: 893 Cov.: 32 AF XY: 0.106 AC XY: 7914 AN XY: 74386

African (AFR) AF: 0.0572 AC: 2374 AN: 41530

American (AMR) AF: 0.138 AC: 2110 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3470

East Asian (EAS) AF: 0.0189 AC: 98 AN: 5184

South Asian (SAS) AF: 0.131 AC: 633 AN: 4822

European-Finnish (FIN) AF: 0.130 AC: 1370 AN: 10570

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8408 AN: 68000

Other (OTH) AF: 0.114 AC: 240 AN: 2112

Alfa AF: 0.117 Hom.: 232

Bravo AF: 0.101

Asia WGS AF: 0.126 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.34
PhyloP100		-0.48
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: rs11616429; hg19: chr13-26552606;