chr2-218337761-G-A

Variant names:

• chr2-218337761-G-A
• rs12471773
• NM_015488.5:c.237-2022G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015488.5(PNKD):​c.237-2022G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,058 control chromosomes in the GnomAD database, including 3,035 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3035 hom., cov: 31)
• Consequence: PNKD NM_015488.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892
• Publications: 13 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNKD	NM_015488.5	c.237-2022G>A		intron_variant	Intron 2 of 9	ENST00000273077.9	NP_056303.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.237-2022G>A		intron_variant	Intron 2 of 9	1	NM_015488.5	ENSP00000273077.4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29646 AN: 151940 Hom.: 3038 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.195 AC: 29652 AN: 152058 Hom.: 3035 Cov.: 31 AF XY: 0.192 AC XY: 14239 AN XY: 74326

African (AFR) AF: 0.179 AC: 7419 AN: 41452

American (AMR) AF: 0.251 AC: 3827 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3470

East Asian (EAS) AF: 0.121 AC: 624 AN: 5170

South Asian (SAS) AF: 0.0903 AC: 435 AN: 4818

European-Finnish (FIN) AF: 0.137 AC: 1451 AN: 10582

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14307 AN: 67994

Other (OTH) AF: 0.228 AC: 480 AN: 2106

Alfa AF: 0.212 Hom.: 6944

Bravo AF: 0.207

Asia WGS AF: 0.102 AC: 355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.96
DANN	Benign	0.61
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12471773; hg19: chr2-219202484;