Genetic Variant PNKD:c.618-58C>T (chr2-218341923-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015488.5(PNKD):c.618-58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,389,250 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 10 hom. )

Consequence

PNKD
NM_015488.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0670

Publications

0 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]

PNKD links:

MIR6810 (HGNC:49987): (microRNA 6810) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6810 links:

CATIP-AS2 (HGNC:41079): (CATIP antisense RNA 2)

CATIP-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-218341923-C-T is Benign according to our data. Variant chr2-218341923-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1219889.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00781 (1189/152322) while in subpopulation AFR AF = 0.0268 (1116/41580). AF 95% confidence interval is 0.0255. There are 16 homozygotes in GnomAd4. There are 569 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1189 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015488.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PNKD	NM_015488.5	MANE Select	c.618-58C>T	intron	N/A	NP_056303.3
PNKD	NM_022572.4		c.546-58C>T	intron	N/A	NP_072094.1	Q8N490-3
MIR6810	NR_106868.1		n.13C>T	non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PNKD	ENST00000273077.9	TSL:1 MANE Select	c.618-58C>T	intron	N/A	ENSP00000273077.4	Q8N490-1
PNKD	ENST00000258362.7	TSL:1	c.546-58C>T	intron	N/A	ENSP00000258362.3	Q8N490-3
PNKD	ENST00000685415.1		c.735-58C>T	intron	N/A	ENSP00000510415.1	A0A8I5KXK0

Frequencies

GnomAD3 genomes

AF:

0.00783

AC:

1191

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

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:

0.0000882

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00225

AC:

528

AN:

234888

AF XY:

0.00174

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000479

Gnomad OTH exome

AF:

0.000513

GnomAD4 exome

AF:

0.000825

AC:

1021

AN:

1236928

Hom.:

Cov.:

AF XY:

0.000705

AC XY:

441

AN XY:

625162

show subpopulations

African (AFR)

AF:

0.0272

AC:

790

AN:

29094

American (AMR)

AF:

0.00227

AC:

AN:

42814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24566

East Asian (EAS)

AF:

0.00

AC:

AN:

38448

South Asian (SAS)

AF:

0.0000495

AC:

AN:

80844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52882

Middle Eastern (MID)

AF:

0.000401

AC:

AN:

4984

European-Non Finnish (NFE)

AF:

0.0000308

AC:

AN:

910158

Other (OTH)

AF:

0.00188

AC:

100

AN:

53138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00781

AC:

1189

AN:

152322

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

569

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0268

AC:

1116

AN:

41580

American (AMR)

AF:

0.00392

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68022

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

122

183

244

305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00658

Hom.:

Bravo

AF:

0.00959

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.5

(source)

DANN

Benign

0.34

PhyloP100

0.067

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over