2-29061812-G-A

Position:

• chr2-29061812-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001029883.3(PCARE):​c.*3057C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0491 in 152,224 control chromosomes in the GnomAD database, including 277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (277 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: PCARE NM_001029883.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.27

Genes affected

PCARE (HGNC:34383): (photoreceptor cilium actin regulator) The protein encoded by this gene is highly expressed in photoreceptors and may associate with the primary cilium of the outer segment. The encoded protein appears to undergo post-translational lipid modification. Nonsense and missense variants of this gene appear to cause a recessive form of retinitis pigmentosa. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-29061812-G-A is Benign according to our data. Variant chr2-29061812-G-A is described in ClinVar as [Benign]. Clinvar id is 335569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCARE	NM_001029883.3	c.*3057C>T		3_prime_UTR_variant	2/2	ENST00000331664.6	NP_001025054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCARE	ENST00000331664.6	c.*3057C>T		3_prime_UTR_variant	2/2	2	NM_001029883.3	ENSP00000332809	P1
PCARE	ENST00000602958.1	n.344C>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7451 AN: 152096 Hom.: 275 Cov.: 32

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0509

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0402

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0491 AC: 7470 AN: 152214 Hom.: 277 Cov.: 32 AF XY: 0.0487 AC XY: 3621 AN XY: 74400

Gnomad4 AFR AF: 0.0919

Gnomad4 AMR AF: 0.0323

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0508

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0273

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0331 Hom.: 29

Bravo AF: 0.0515

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.31

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: rs75634215; hg19: chr2-29284678;