chr2-218339877-A-C

Position:

• chr2-218339877-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015488.5(PNKD):​c.331A>C​(p.Thr111Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PNKD NM_015488.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074816346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNKD	NM_015488.5	c.331A>C	p.Thr111Pro	missense_variant	3/10	ENST00000273077.9	NP_056303.3
CATIP-AS2	NR_125777.1	n.120+11283T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.331A>C	p.Thr111Pro	missense_variant	3/10	1	NM_015488.5	ENSP00000273077
CATIP-AS2	ENST00000411433.1	n.120+11283T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 18 AN: 149808 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000239

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0507 AC: 8381 AN: 165384 Hom.: 0 AF XY: 0.0580 AC XY: 5131 AN XY: 88512

Gnomad AFR exome AF: 0.0468

Gnomad AMR exome AF: 0.0283

Gnomad ASJ exome AF: 0.0450

Gnomad EAS exome AF: 0.0308

Gnomad SAS exome AF: 0.0544

Gnomad FIN exome AF: 0.0636

Gnomad NFE exome AF: 0.0620

Gnomad OTH exome AF: 0.0312

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00426 AC: 5956 AN: 1398740 Hom.: 0 Cov.: 31 AF XY: 0.00553 AC XY: 3814 AN XY: 690310

Gnomad4 AFR exome AF: 0.00266

Gnomad4 AMR exome AF: 0.0195

Gnomad4 ASJ exome AF: 0.00763

Gnomad4 EAS exome AF: 0.00500

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.00267

Gnomad4 OTH exome AF: 0.00236

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000133 AC: 20 AN: 149910 Hom.: 0 Cov.: 31 AF XY: 0.000192 AC XY: 14 AN XY: 73054

Gnomad4 AFR AF: 0.0000490

Gnomad4 AMR AF: 0.0000662

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000239

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0109 Hom.: 0

ExAC AF: 0.00357 AC: 431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.67	T;T;T
MetaRNN	Benign	0.0075	T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.98	N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.25
MPC		0.18
ClinPred		0.0090	T
GERP RS		-0.12
Varity_R		0.16
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs202190131; hg19: chr2-219204600; COSMIC: COSV51230896; COSMIC: COSV51230896;