2-29062199-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001029883.3(PCARE):c.*2670T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,126 control chromosomes in the GnomAD database, including 56,524 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.84 (56503 hom., cov: 31)
  • Exomes 𝑓: 0.94 (21 hom.)
• Consequence: PCARE NM_001029883.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.258

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-29062199-A-G is Benign according to our data. Variant chr2-29062199-A-G is described in ClinVar as [Benign]. Clinvar id is 335576.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCARE	NM_001029883.3	c.*2670T>C		3_prime_UTR_variant	2/2	ENST00000331664.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCARE	ENST00000331664.6	c.*2670T>C		3_prime_UTR_variant	2/2	2	NM_001029883.3	P1
PCARE	ENST00000602958.1			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127976 AN: 151960 Hom.: 56493 Cov.: 31

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.886

GnomAD4 exome AF: 0.938 AC: 45 AN: 48 Hom.: 21 Cov.: 0 AF XY: 0.964 AC XY: 27 AN XY: 28

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.967

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.842 AC: 128023 AN: 152078 Hom.: 56503 Cov.: 31 AF XY: 0.845 AC XY: 62845 AN XY: 74346

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.921

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.937

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.964

Gnomad4 OTH AF: 0.887

Alfa AF: 0.917 Hom.: 8882

Bravo AF: 0.826

Asia WGS AF: 0.907 AC: 3157 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.90
Cadd	Benign	2.2
Dann	Benign	0.50

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: rs10185075; hg19: chr2-29285065;