NM_001029883.3:c.*2754A>G

Variant names:

• chr2-29062115-T-C
• rs10187620
• NM_001029883.3:c.*2754A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001029883.3(PCARE):​c.*2754A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,098 control chromosomes in the GnomAD database, including 27,093 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (27086 hom., cov: 32)
  • Exomes 𝑓: 0.55 (7 hom.)
• Consequence: PCARE NM_001029883.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-29062115-T-C is Benign according to our data. Variant chr2-29062115-T-C is described in ClinVar as Benign. ClinVar VariationId is 335575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

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.*2754A>G		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.*2754A>G		3_prime_UTR	Exon 2 of 2	ENSP00000332809.4	A6NGG8
	PCARE	ENST00000602958.1	TSL:4	n.41A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86326 AN: 151920 Hom.: 27071 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.619

GnomAD4 exome AF: 0.554 AC: 31 AN: 56 Hom.: 7 Cov.: 0 AF XY: 0.536 AC XY: 15 AN XY: 28

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) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.575 AC: 23 AN: 40

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.568 AC: 86366 AN: 152042 Hom.: 27086 Cov.: 32 AF XY: 0.566 AC XY: 42047 AN XY: 74310

African (AFR) AF: 0.293 AC: 12146 AN: 41470

American (AMR) AF: 0.687 AC: 10505 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2321 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2161 AN: 5148

South Asian (SAS) AF: 0.628 AC: 3027 AN: 4818

European-Finnish (FIN) AF: 0.607 AC: 6421 AN: 10572

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47904 AN: 67966

Other (OTH) AF: 0.615 AC: 1298 AN: 2112

Alfa AF: 0.661 Hom.: 83725

Bravo AF: 0.560

Asia WGS AF: 0.512 AC: 1787 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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	-0.91
CADD	Benign	0.22
DANN	Benign	0.47
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs10187620; hg19: chr2-29284981;