chr2-29061940-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001029883.3(PCARE):​c.*2929T>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 0.935 in 152,246 control chromosomes in the GnomAD database, including 67,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67351 hom., cov: 32)
Exomes 𝑓: 1.0 ( 9 hom. )

Consequence

PCARE
NM_001029883.3 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.498
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
Variant 2-29061940-A-G is Benign according to our data. Variant chr2-29061940-A-G is described in ClinVar as [Benign]. Clinvar id is 335573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PCARENM_001029883.3 linkuse as main transcriptc.*2929T>C 3_prime_UTR_variant 2/2 ENST00000331664.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PCAREENST00000331664.6 linkuse as main transcriptc.*2929T>C 3_prime_UTR_variant 2/22 NM_001029883.3 P1
PCAREENST00000602958.1 linkuse as main transcriptn.216T>C non_coding_transcript_exon_variant 1/34

Frequencies

GnomAD3 genomes
AF:
0.936
AC:
142308
AN:
152110
Hom.:
67326
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.776
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.978
Gnomad ASJ
AF:
0.996
Gnomad EAS
AF:
0.997
Gnomad SAS
AF:
0.999
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
0.984
Gnomad NFE
AF:
0.999
Gnomad OTH
AF:
0.962
GnomAD4 exome
AF:
1.00
AC:
18
AN:
18
Hom.:
9
Cov.:
0
AF XY:
1.00
AC XY:
6
AN XY:
6
show subpopulations
Gnomad4 FIN exome
AF:
1.00
Gnomad4 NFE exome
AF:
1.00
GnomAD4 genome
AF:
0.935
AC:
142386
AN:
152228
Hom.:
67351
Cov.:
32
AF XY:
0.937
AC XY:
69761
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.775
Gnomad4 AMR
AF:
0.978
Gnomad4 ASJ
AF:
0.996
Gnomad4 EAS
AF:
0.997
Gnomad4 SAS
AF:
0.999
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
0.999
Gnomad4 OTH
AF:
0.963
Alfa
AF:
0.959
Hom.:
13340
Bravo
AF:
0.927
Asia WGS
AF:
0.979
AC:
3406
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Retinitis pigmentosa Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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
-0.94
CADD
Benign
3.1
DANN
Benign
0.54

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11683284; hg19: chr2-29284806; API