Genetic Variant ATP13A2:c.1195+66A>G (chr1-16996954-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022089.4(ATP13A2):c.1195+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 1,566,436 control chromosomes in the GnomAD database, including 530,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 49717 hom., cov: 32)

Exomes 𝑓: 0.82 ( 481197 hom. )

Consequence

ATP13A2
NM_022089.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.18

Variant links:

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]

ATP13A2 links:

ENSG00000226526 (HGNC:):

ENSG00000226526 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 1-16996954-T-C is Benign according to our data. Variant chr1-16996954-T-C is described in ClinVar as [Benign]. Clinvar id is 1192485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16996954-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP13A2	NM_022089.4 link	c.1195+66A>G		intron_variant	Intron 12 of 28	ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13 link	c.1195+66A>G		intron_variant	Intron 12 of 28	1	NM_022089.4	ENSP00000327214.8		Q9NQ11-1

Frequencies

GnomAD3 genomes

AF:

0.807

AC:

122642

AN:

152014

Hom.:

49690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.798

Gnomad AMR

AF:

0.872

Gnomad ASJ

AF:

0.818

Gnomad EAS

AF:

0.846

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.845

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.824

Gnomad OTH

AF:

0.821

GnomAD4 exome

AF:

0.824

AC:

1165591

AN:

1414304

Hom.:

481197

AF XY:

0.822

AC XY:

575821

AN XY:

700902

show subpopulations

Gnomad4 AFR exome

AF:

0.747

Gnomad4 AMR exome

AF:

0.884

Gnomad4 ASJ exome

AF:

0.813

Gnomad4 EAS exome

AF:

0.841

Gnomad4 SAS exome

AF:

0.749

Gnomad4 FIN exome

AF:

0.841

Gnomad4 NFE exome

AF:

0.829

Gnomad4 OTH exome

AF:

0.819

GnomAD4 genome

AF:

0.807

AC:

122716

AN:

152132

Hom.:

49717

Cov.:

AF XY:

0.807

AC XY:

60039

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.746

Gnomad4 AMR

AF:

0.873

Gnomad4 ASJ

AF:

0.818

Gnomad4 EAS

AF:

0.846

Gnomad4 SAS

AF:

0.737

Gnomad4 FIN

AF:

0.845

Gnomad4 NFE

AF:

0.824

Gnomad4 OTH

AF:

0.813

Alfa

AF:

0.770

Hom.:

3321

Bravo

AF:

0.808

Asia WGS

AF:

0.745

AC:

2590

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 93. Only high quality variants are reported. -

Autosomal recessive spastic paraplegia type 78

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Kufor-Rakeb syndrome

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.84

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over