chr2-29062307-C-G

Variant names:

• chr2-29062307-C-G
• rs188247308
• NM_001029883.3:c.*2562G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001029883.3(PCARE):​c.*2562G>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 0.006 in 152,376 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0060 (2 hom., cov: 33)
  • Exomes 𝑓: 0.022 (0 hom.)
• Consequence: PCARE NM_001029883.3 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.372
• Publications: 1 publications found

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]

PCARE Gene-Disease associations (from GenCC):

• PCARE-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 54

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-29062307-C-G is Benign according to our data. Variant chr2-29062307-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 335581.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.006 (913/152284) while in subpopulation NFE AF = 0.0104 (709/68022). AF 95% confidence interval is 0.00979. There are 2 homozygotes in GnomAd4. There are 416 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029883.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCARE	NM_001029883.3	MANE Select	c.*2562G>C		3_prime_UTR	Exon 2 of 2	NP_001025054.1	A6NGG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCARE	ENST00000331664.6	TSL:2 MANE Select	c.*2562G>C		3_prime_UTR	Exon 2 of 2	ENSP00000332809.4	A6NGG8
	PCARE	ENST00000602958.1	TSL:4	n.-152G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00600 AC: 913 AN: 152166 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.0217 AC: 2 AN: 92 Hom.: 0 Cov.: 0 AF XY: 0.0139 AC XY: 1 AN XY: 72

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0244 AC: 2 AN: 82

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.00600 AC: 913 AN: 152284 Hom.: 2 Cov.: 33 AF XY: 0.00559 AC XY: 416 AN XY: 74456

African (AFR) AF: 0.00168 AC: 70 AN: 41548

American (AMR) AF: 0.00529 AC: 81 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4826

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0104 AC: 709 AN: 68022

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00204 Hom.: 0

Bravo AF: 0.00553

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.45
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs188247308; hg19: chr2-29285173;