rs34014804

Variant names:

• chr2-218340748-G-A
• rs34014804
• NM_015488.5:c.486G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015488.5(PNKD):​c.486G>A​(p.Gly162Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,613,360 control chromosomes in the GnomAD database, including 1,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G162G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.062 (349 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1626 hom.)
• Consequence: PNKD NM_015488.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.49
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-218340748-G-A is Benign according to our data. Variant chr2-218340748-G-A is described in ClinVar as Benign. ClinVar VariationId is 260662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	NM_015488.5	MANE Select	c.486G>A	p.Gly162Gly	synonymous	Exon 5 of 10	NP_056303.3
	PNKD	NM_022572.4		c.414G>A	p.Gly138Gly	synonymous	Exon 4 of 9	NP_072094.1	Q8N490-3
	CATIP-AS2	NR_125777.1		n.120+10412C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	ENST00000273077.9	TSL:1 MANE Select	c.486G>A	p.Gly162Gly	synonymous	Exon 5 of 10	ENSP00000273077.4	Q8N490-1
	PNKD	ENST00000258362.7	TSL:1	c.414G>A	p.Gly138Gly	synonymous	Exon 4 of 9	ENSP00000258362.3	Q8N490-3
	PNKD	ENST00000685415.1		c.603G>A	p.Gly201Gly	synonymous	Exon 6 of 11	ENSP00000510415.1	A0A8I5KXK0

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9405 AN: 152008 Hom.: 348 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0848

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.00310

Gnomad SAS AF: 0.0237

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.0618

GnomAD2 exomes AF: 0.0432 AC: 10863 AN: 251456 AF XY: 0.0426

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0344

Gnomad ASJ exome AF: 0.0888

Gnomad EAS exome AF: 0.00234

Gnomad FIN exome AF: 0.0343

Gnomad NFE exome AF: 0.0463

Gnomad OTH exome AF: 0.0493

GnomAD4 exome AF: 0.0431 AC: 63009 AN: 1461234 Hom.: 1626 Cov.: 31 AF XY: 0.0430 AC XY: 31248 AN XY: 726932

African (AFR) AF: 0.103 AC: 3438 AN: 33456

American (AMR) AF: 0.0369 AC: 1650 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0881 AC: 2301 AN: 26128

East Asian (EAS) AF: 0.00131 AC: 52 AN: 39696

South Asian (SAS) AF: 0.0240 AC: 2073 AN: 86254

European-Finnish (FIN) AF: 0.0322 AC: 1718 AN: 53396

Middle Eastern (MID) AF: 0.0651 AC: 375 AN: 5764

European-Non Finnish (NFE) AF: 0.0438 AC: 48684 AN: 1111440

Other (OTH) AF: 0.0450 AC: 2718 AN: 60378

GnomAD4 genome AF: 0.0619 AC: 9416 AN: 152126 Hom.: 349 Cov.: 32 AF XY: 0.0605 AC XY: 4496 AN XY: 74366

African (AFR) AF: 0.105 AC: 4374 AN: 41500

American (AMR) AF: 0.0508 AC: 775 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3472

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5154

South Asian (SAS) AF: 0.0241 AC: 116 AN: 4816

European-Finnish (FIN) AF: 0.0374 AC: 396 AN: 10598

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0470 AC: 3198 AN: 68008

Other (OTH) AF: 0.0607 AC: 128 AN: 2108

Alfa AF: 0.0616 Hom.: 289

Bravo AF: 0.0649

Asia WGS AF: 0.0270 AC: 94 AN: 3478

EpiCase AF: 0.0552

EpiControl AF: 0.0560

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Paroxysmal nonkinesigenic dyskinesia 1 (2)
-	-	1	not specified (1)
-	-	1	Paroxysmal nonkinesigenic dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.82
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs34014804; hg19: chr2-219205471;