rs9076

Variant names:

• chr2-218346058-G-A
• rs9076
• NM_015488.5:c.*1077G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015488.5(PNKD):​c.*1077G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,204 control chromosomes in the GnomAD database, including 17,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (17030 hom., cov: 33)
  • Exomes 𝑓: 0.54 (21 hom.)
• Consequence: PNKD NM_015488.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.166
• Publications: 21 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-218346058-G-A is Benign according to our data. Variant chr2-218346058-G-A is described in ClinVar as Benign. ClinVar VariationId is 334345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 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.*1077G>A		3_prime_UTR	Exon 10 of 10	NP_056303.3
	PNKD	NM_022572.4		c.*1077G>A		3_prime_UTR	Exon 9 of 9	NP_072094.1	Q8N490-3
	CATIP-AS2	NR_125777.1		n.120+5102C>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.*1077G>A		3_prime_UTR	Exon 10 of 10	ENSP00000273077.4	Q8N490-1
	PNKD	ENST00000258362.7	TSL:1	c.*1077G>A		3_prime_UTR	Exon 9 of 9	ENSP00000258362.3	Q8N490-3
	PNKD	ENST00000685415.1		c.*1077G>A		3_prime_UTR	Exon 11 of 11	ENSP00000510415.1	A0A8I5KXK0

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67887 AN: 151924 Hom.: 17022 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.544 AC: 87 AN: 160 Hom.: 21 Cov.: 0 AF XY: 0.523 AC XY: 46 AN XY: 88

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.558 AC: 77 AN: 138

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.450 AC: 9 AN: 20

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.447 AC: 67904 AN: 152044 Hom.: 17030 Cov.: 33 AF XY: 0.453 AC XY: 33659 AN XY: 74342

African (AFR) AF: 0.198 AC: 8213 AN: 41482

American (AMR) AF: 0.526 AC: 8037 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1642 AN: 3470

East Asian (EAS) AF: 0.629 AC: 3244 AN: 5160

South Asian (SAS) AF: 0.588 AC: 2837 AN: 4826

European-Finnish (FIN) AF: 0.597 AC: 6304 AN: 10562

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36152 AN: 67952

Other (OTH) AF: 0.464 AC: 981 AN: 2112

Alfa AF: 0.502 Hom.: 69589

Bravo AF: 0.427

Asia WGS AF: 0.620 AC: 2156 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.43
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs9076; hg19: chr2-219210781; COSMIC: COSV51243078; COSMIC: COSV51243078;