rs56010635

Positions:

• chr1-16991598-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022089.4(ATP13A2):​c.2251+136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,307,398 control chromosomes in the GnomAD database, including 3 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 0.0019 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: ATP13A2 NM_022089.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

Genes affected

ATP13A2 (HGNC:30213): (ATPase cation transporting 13A2) This gene encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. Mutations in this gene are associated with Kufor-Rakeb syndrome (KRS), also referred to as Parkinson disease 9. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2008]

ENSG00000226526 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00186 (284/152290) while in subpopulation AFR AF= 0.00599 (249/41558). AF 95% confidence interval is 0.00538. There are 3 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A2	NM_022089.4	c.2251+136C>T		intron_variant		ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13	c.2251+136C>T		intron_variant		1	NM_022089.4	ENSP00000327214.8

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 284 AN: 152172 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00601

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000284 AC: 328 AN: 1155108 Hom.: 0 AF XY: 0.000257 AC XY: 150 AN XY: 583892

Gnomad4 AFR exome AF: 0.00640

Gnomad4 AMR exome AF: 0.000890

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000529

Gnomad4 SAS exome AF: 0.0000254

Gnomad4 FIN exome AF: 0.0000226

Gnomad4 NFE exome AF: 0.0000922

Gnomad4 OTH exome AF: 0.000540

GnomAD4 genome AF: 0.00186 AC: 284 AN: 152290 Hom.: 3 Cov.: 33 AF XY: 0.00154 AC XY: 115 AN XY: 74478

Gnomad4 AFR AF: 0.00599

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00173 Hom.: 0

Bravo AF: 0.00207

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.60

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: rs56010635; hg19: chr1-17318093;