2-178453333-C-T

Position:

• chr2-178453333-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000375129.8(PJVK):​c.-77C>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 0.00108 in 1,438,228 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (10 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (7 hom.)
• Consequence: PJVK ENST00000375129.8 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.365

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-178453333-C-T is Benign according to our data. Variant chr2-178453333-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1214892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00546 (831/152272) while in subpopulation AFR AF= 0.0192 (798/41546). AF 95% confidence interval is 0.0181. There are 10 homozygotes in gnomad4. There are 399 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PJVK	NM_001042702.5	c.-22-55C>T		intron_variant		ENST00000644580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PJVK	ENST00000644580.2	c.-22-55C>T		intron_variant			NM_001042702.5	P1

Frequencies

GnomAD3 genomes AF: 0.00544 AC: 827 AN: 152154 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000559 AC: 719 AN: 1285956 Hom.: 7 Cov.: 18 AF XY: 0.000467 AC XY: 303 AN XY: 648238

Gnomad4 AFR exome AF: 0.0202

Gnomad4 AMR exome AF: 0.000950

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000621

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000146

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.00546 AC: 831 AN: 152272 Hom.: 10 Cov.: 33 AF XY: 0.00536 AC XY: 399 AN XY: 74460

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00354 Hom.: 1

Bravo AF: 0.00662

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.3
DANN	Benign	0.78

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: rs77758075; hg19: chr2-179318060;