NM_001029883.3:c.*2670T>C

Variant names:

• chr2-29062199-A-G
• rs10185075
• NM_001029883.3:c.*2670T>C

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.258
• Publications: 3 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=-0.9).
• BP6: Variant 2-29062199-A-G is Benign according to our data. Variant chr2-29062199-A-G is described in ClinVar as Benign. ClinVar VariationId is 335576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.958 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.*2670T>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.*2670T>C		3_prime_UTR	Exon 2 of 2	ENSP00000332809.4	A6NGG8
	PCARE	ENST00000602958.1	TSL:4	n.-44T>C		upstream_gene	N/A

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

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 1.00 AC: 6 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.967 AC: 29 AN: 30

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

African (AFR) AF: 0.546 AC: 22632 AN: 41414

American (AMR) AF: 0.921 AC: 14085 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 3401 AN: 3472

East Asian (EAS) AF: 0.937 AC: 4827 AN: 5150

South Asian (SAS) AF: 0.937 AC: 4516 AN: 4818

European-Finnish (FIN) AF: 0.953 AC: 10108 AN: 10606

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65553 AN: 68008

Other (OTH) AF: 0.887 AC: 1871 AN: 2110

Alfa AF: 0.777 Hom.: 10952

Bravo AF: 0.826

Asia WGS AF: 0.907 AC: 3157 AN: 3478

ClinVar

ClinVar submissions

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	-0.90
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		0.26
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: rs10185075; hg19: chr2-29285065;