chr2-218340005-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015488.5(PNKD):​c.353-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 1,554,528 control chromosomes in the GnomAD database, including 3,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 320 hom., cov: 31)
Exomes 𝑓: 0.058 ( 2955 hom. )

Consequence

PNKD
NM_015488.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.891

Publications

3 publications found
Variant links:
Genes affected
PNKD (HGNC:9153): (PNKD metallo-beta-lactamase domain containing) This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
CATIP-AS2 (HGNC:41079): (CATIP antisense RNA 2)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 2-218340005-C-T is Benign according to our data. Variant chr2-218340005-C-T is described in ClinVar as [Benign]. Clinvar id is 260660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PNKDNM_015488.5 linkc.353-24C>T intron_variant Intron 3 of 9 ENST00000273077.9 NP_056303.3 Q8N490-1A0A024R415

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PNKDENST00000273077.9 linkc.353-24C>T intron_variant Intron 3 of 9 1 NM_015488.5 ENSP00000273077.4 Q8N490-1

Frequencies

GnomAD3 genomes
AF:
0.0548
AC:
8335
AN:
152104
Hom.:
320
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0400
Gnomad AMI
AF:
0.0285
Gnomad AMR
AF:
0.0390
Gnomad ASJ
AF:
0.0449
Gnomad EAS
AF:
0.167
Gnomad SAS
AF:
0.141
Gnomad FIN
AF:
0.0672
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.0518
Gnomad OTH
AF:
0.0531
GnomAD2 exomes
AF:
0.0675
AC:
16898
AN:
250348
AF XY:
0.0704
show subpopulations
Gnomad AFR exome
AF:
0.0361
Gnomad AMR exome
AF:
0.0368
Gnomad ASJ exome
AF:
0.0448
Gnomad EAS exome
AF:
0.165
Gnomad FIN exome
AF:
0.0667
Gnomad NFE exome
AF:
0.0509
Gnomad OTH exome
AF:
0.0574
GnomAD4 exome
AF:
0.0577
AC:
80852
AN:
1402306
Hom.:
2955
Cov.:
25
AF XY:
0.0602
AC XY:
42251
AN XY:
701294
show subpopulations
African (AFR)
AF:
0.0410
AC:
1320
AN:
32222
American (AMR)
AF:
0.0369
AC:
1649
AN:
44640
Ashkenazi Jewish (ASJ)
AF:
0.0407
AC:
1048
AN:
25760
East Asian (EAS)
AF:
0.123
AC:
4845
AN:
39374
South Asian (SAS)
AF:
0.131
AC:
11095
AN:
84994
European-Finnish (FIN)
AF:
0.0712
AC:
3801
AN:
53350
Middle Eastern (MID)
AF:
0.0646
AC:
365
AN:
5652
European-Non Finnish (NFE)
AF:
0.0501
AC:
53001
AN:
1057852
Other (OTH)
AF:
0.0638
AC:
3728
AN:
58462
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
4327
8653
12980
17306
21633
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2024
4048
6072
8096
10120
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0547
AC:
8332
AN:
152222
Hom.:
320
Cov.:
31
AF XY:
0.0574
AC XY:
4270
AN XY:
74412
show subpopulations
African (AFR)
AF:
0.0401
AC:
1665
AN:
41542
American (AMR)
AF:
0.0388
AC:
594
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.0449
AC:
156
AN:
3472
East Asian (EAS)
AF:
0.167
AC:
861
AN:
5162
South Asian (SAS)
AF:
0.141
AC:
677
AN:
4806
European-Finnish (FIN)
AF:
0.0672
AC:
713
AN:
10618
Middle Eastern (MID)
AF:
0.0272
AC:
8
AN:
294
European-Non Finnish (NFE)
AF:
0.0518
AC:
3522
AN:
68012
Other (OTH)
AF:
0.0521
AC:
110
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
394
788
1182
1576
1970
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
100
200
300
400
500
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0487
Hom.:
109
Bravo
AF:
0.0507
Asia WGS
AF:
0.126
AC:
438
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Aug 21, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
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
-0.81
CADD
Benign
6.9
DANN
Benign
0.69
PhyloP100
0.89
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs73088163; hg19: chr2-219204728; COSMIC: COSV51232295; COSMIC: COSV51232295; API