rs886055210

Variant names:

• chr2-178451728-C-T
• rs886055210
• NM_001042702.5:c.-64C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001042702.5(PJVK):​c.-64C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000194 in 977,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: PJVK NM_001042702.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.171
• Publications: 0 publications found

Genes affected

PJVK (HGNC:29502): (pejvakin) The protein encoded by this gene is a member of the gasdermin family, a family which is found only in vertebrates. The encoded protein is required for the proper function of auditory pathway neurons. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal recessive type 59 (DFNB59). [provided by RefSeq, Dec 2008]

PRKRA (HGNC:9438): (protein activator of interferon induced protein kinase EIF2AK2) This gene encodes a protein kinase activated by double-stranded RNA which mediates the effects of interferon in response to viral infection. Mutations in this gene have been associated with dystonia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

PRKRA Gene-Disease associations (from GenCC):

• dystonia 16

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042702.5. 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
	PJVK	NM_001042702.5	MANE Select	c.-64C>T		5_prime_UTR	Exon 1 of 7	NP_001036167.1	Q0ZLH3
	PJVK	NM_001353775.2		c.-113C>T		5_prime_UTR	Exon 1 of 7	NP_001340704.1
	PJVK	NM_001353777.1		c.-376C>T		5_prime_UTR	Exon 1 of 7	NP_001340706.1	A0PK15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PJVK	ENST00000644580.2	MANE Select	c.-64C>T		5_prime_UTR	Exon 1 of 7	ENSP00000495855.2	Q0ZLH3
	PJVK	ENST00000970493.1		c.-176C>T		5_prime_UTR	Exon 1 of 8	ENSP00000640552.1
	PJVK	ENST00000642492.1		c.-599C>T		5_prime_UTR	Exon 1 of 8	ENSP00000496267.1	A0PK15

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000145 AC: 12 AN: 825438 Hom.: 0 Cov.: 16 AF XY: 0.0000210 AC XY: 8 AN XY: 381476

African (AFR) AF: 0.000512 AC: 8 AN: 15630

American (AMR) AF: 0.00 AC: 0 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5100

East Asian (EAS) AF: 0.00 AC: 0 AN: 3596

South Asian (SAS) AF: 0.00 AC: 0 AN: 16288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1596

European-Non Finnish (NFE) AF: 0.00000265 AC: 2 AN: 754928

Other (OTH) AF: 0.0000739 AC: 2 AN: 27050

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74464

African (AFR) AF: 0.000168 AC: 7 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal recessive nonsyndromic hearing loss 59 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		0.17
PromoterAI		0.0020	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs886055210; hg19: chr2-179316455;