rs4920608

Positions:

• chr1-16992792-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022089.4(ATP13A2):​c.1750-211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,190 control chromosomes in the GnomAD database, including 23,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.55 (23538 hom., cov: 35)
• Consequence: ATP13A2 NM_022089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.279

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-16992792-C-T is Benign according to our data. Variant chr1-16992792-C-T is described in ClinVar as [Benign]. Clinvar id is 1238030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A2	NM_022089.4	c.1750-211G>A		intron_variant		ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13	c.1750-211G>A		intron_variant		1	NM_022089.4	ENSP00000327214	A1
	ENST00000446261.1	n.188-11851C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83295 AN: 152072 Hom.: 23530 Cov.: 35

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.548 AC: 83332 AN: 152190 Hom.: 23538 Cov.: 35 AF XY: 0.540 AC XY: 40144 AN XY: 74396

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.549

Alfa AF: 0.610 Hom.: 27490

Bravo AF: 0.544

Asia WGS AF: 0.369 AC: 1285 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.5
DANN	Benign	0.84

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: rs4920608; hg19: chr1-17319287;