1-16996954-T-C

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

2

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]

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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
ATP13A2NM_022089.4 linkc.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
ATP13A2ENST00000326735.13 linkc.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.:
32
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.:
32
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.

Other links and lift over

dbSNP: rs9435736; hg19: chr1-17323449; API