2-218341923-C-T

Position:

• chr2-218341923-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015488.5(PNKD):​c.618-58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,389,250 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (10 hom.)
• Consequence: PNKD NM_015488.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0670

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]

MIR6810 (HGNC:49987): (microRNA 6810) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

CATIP-AS2 (HGNC:41079): (CATIP antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-218341923-C-T is Benign according to our data. Variant chr2-218341923-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00781 (1189/152322) while in subpopulation AFR AF= 0.0268 (1116/41580). AF 95% confidence interval is 0.0255. There are 16 homozygotes in gnomad4. There are 569 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNKD	NM_015488.5	c.618-58C>T		intron_variant		ENST00000273077.9	NP_056303.3
MIR6810	NR_106868.1	n.13C>T		non_coding_transcript_exon_variant	1/1
CATIP-AS2	NR_125777.1	n.120+9237G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.618-58C>T		intron_variant		1	NM_015488.5	ENSP00000273077
MIR6810	ENST00000622701.1	n.13C>T		mature_miRNA_variant	1/1
CATIP-AS2	ENST00000411433.1	n.120+9237G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00783 AC: 1191 AN: 152204 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00225 AC: 528 AN: 234888 Hom.: 5 AF XY: 0.00174 AC XY: 221 AN XY: 127080

Gnomad AFR exome AF: 0.0298

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000683

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000479

Gnomad OTH exome AF: 0.000513

GnomAD4 exome AF: 0.000825 AC: 1021 AN: 1236928 Hom.: 10 Cov.: 17 AF XY: 0.000705 AC XY: 441 AN XY: 625162

Gnomad4 AFR exome AF: 0.0272

Gnomad4 AMR exome AF: 0.00227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000495

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000308

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.00781 AC: 1189 AN: 152322 Hom.: 16 Cov.: 32 AF XY: 0.00764 AC XY: 569 AN XY: 74482

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00466 Hom.: 1

Bravo AF: 0.00959

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 23, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.34

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: rs74718922; hg19: chr2-219206646;