2-218340003-C-T

Variant names:

• chr2-218340003-C-T
• rs201632828
• NM_015488.5:c.353-26C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_015488.5(PNKD):​c.353-26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00385 in 1,547,212 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0040 (29 hom.)
• Consequence: PNKD NM_015488.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.60
• Publications: 1 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-218340003-C-T is Benign according to our data. Variant chr2-218340003-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 445 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNKD	NM_015488.5	c.353-26C>T		intron_variant	Intron 3 of 9	ENST00000273077.9	NP_056303.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.353-26C>T		intron_variant	Intron 3 of 9	1	NM_015488.5	ENSP00000273077.4

Frequencies

GnomAD3 genomes AF: 0.00293 AC: 445 AN: 152134 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00388

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00328 AC: 822 AN: 250272 AF XY: 0.00313

Gnomad AFR exome AF: 0.000557

Gnomad AMR exome AF: 0.00241

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00764

Gnomad NFE exome AF: 0.00459

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00396 AC: 5519 AN: 1394960 Hom.: 29 Cov.: 24 AF XY: 0.00389 AC XY: 2716 AN XY: 697652

African (AFR) AF: 0.000623 AC: 20 AN: 32120

American (AMR) AF: 0.00226 AC: 101 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.0000389 AC: 1 AN: 25708

East Asian (EAS) AF: 0.00 AC: 0 AN: 39396

South Asian (SAS) AF: 0.00115 AC: 98 AN: 84940

European-Finnish (FIN) AF: 0.00797 AC: 425 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00445 AC: 4677 AN: 1050976

Other (OTH) AF: 0.00338 AC: 197 AN: 58216

GnomAD4 genome AF: 0.00292 AC: 445 AN: 152252 Hom.: 0 Cov.: 31 AF XY: 0.00334 AC XY: 249 AN XY: 74442

African (AFR) AF: 0.000770 AC: 32 AN: 41548

American (AMR) AF: 0.00517 AC: 79 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00584 AC: 62 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00388 AC: 264 AN: 68002

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00287 Hom.: 0

Bravo AF: 0.00277

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.65
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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: rs201632828; hg19: chr2-219204726;