rs187333111

Variant names:

• chr2-29064997-C-T
• rs187333111
• NM_001029883.3:c.3739G>A

Variant summary

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

The NM_001029883.3(PCARE):​c.3739G>A​(p.Gly1247Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00698 in 1,573,766 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0072 (93 hom.)
• Consequence: PCARE NM_001029883.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -2.07

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 (MetaRNN=0.0017879605).
• BP6: Variant 2-29064997-C-T is Benign according to our data. Variant chr2-29064997-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 195107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-29064997-C-T is described in Lovd as [Benign]. Variant chr2-29064997-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00456 (695/152334) while in subpopulation SAS AF= 0.0329 (159/4828). AF 95% confidence interval is 0.0288. There are 4 homozygotes in gnomad4. There are 336 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCARE	NM_001029883.3	c.3739G>A	p.Gly1247Ser	missense_variant	Exon 2 of 2	ENST00000331664.6	NP_001025054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCARE	ENST00000331664.6	c.3739G>A	p.Gly1247Ser	missense_variant	Exon 2 of 2	2	NM_001029883.3	ENSP00000332809.4

Frequencies

GnomAD3 genomes AF: 0.00457 AC: 695 AN: 152216 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00557

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00827 AC: 1470 AN: 177758 Hom.: 27 AF XY: 0.0102 AC XY: 979 AN XY: 95702

Gnomad AFR exome AF: 0.000499

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00598

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0328

Gnomad FIN exome AF: 0.00184

Gnomad NFE exome AF: 0.00668

Gnomad OTH exome AF: 0.00625

GnomAD4 exome AF: 0.00724 AC: 10297 AN: 1421432 Hom.: 93 Cov.: 35 AF XY: 0.00802 AC XY: 5642 AN XY: 703582

Gnomad4 AFR exome AF: 0.000650

Gnomad4 AMR exome AF: 0.00229

Gnomad4 ASJ exome AF: 0.00582

Gnomad4 EAS exome AF: 0.000108

Gnomad4 SAS exome AF: 0.0327

Gnomad4 FIN exome AF: 0.00199

Gnomad4 NFE exome AF: 0.00623

Gnomad4 OTH exome AF: 0.00702

GnomAD4 genome AF: 0.00456 AC: 695 AN: 152334 Hom.: 4 Cov.: 33 AF XY: 0.00451 AC XY: 336 AN XY: 74496

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0329

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00557

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00534 Hom.: 3

Bravo AF: 0.00388

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00126 AC: 5

ESP6500EA AF: 0.00555 AC: 46

ExAC AF: 0.00717 AC: 853

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

May 30, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:2

Dec 18, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Retinitis pigmentosa 54 Benign:2

Aug 30, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 26, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal dystrophy Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Retinitis pigmentosa Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0060
DANN	Benign	0.53
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.95	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.075
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.034
MVP		0.076
MPC		0.013
ClinPred		0.0019	T
GERP RS		-7.2
Varity_R		0.023
gMVP		0.019

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: rs187333111; hg19: chr2-29287863; COSMIC: COSV105234425; COSMIC: COSV105234425;