chr2-218270540-C-G

Variant names:

• chr2-218270540-C-G
• NM_015488.5:c.5C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015488.5(PNKD):​c.5C>G​(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PNKD NM_015488.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNKD	NM_015488.5	c.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 10	ENST00000273077.9	NP_056303.3
PNKD	NM_001077399.3	c.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 3		NP_001070867.1
PNKD	XM_017003771.2	c.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 9		XP_016859260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 10	1	NM_015488.5	ENSP00000273077.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1081160 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 519496

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.80	T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.33	N;N
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.42
MutPred		0.38		Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP		0.90
MPC		0.35
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.47
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219135263;