Genetic Variant PCARE:c.*2585A>G (chr2-29062284-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001029883.3(PCARE):c.*2585A>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 0.985 in 152,424 control chromosomes in the GnomAD database, including 73,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 73869 hom., cov: 32)

Exomes 𝑓: 1.0 ( 77 hom. )

Consequence

PCARE
NM_001029883.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.24

Publications

3 publications found

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]

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

PCARE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 2-29062284-T-C is Benign according to our data. Variant chr2-29062284-T-C is described in ClinVar as Benign. ClinVar VariationId is 335578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.*2585A>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.*2585A>G		3_prime_UTR	Exon 2 of 2	ENSP00000332809.4	A6NGG8
	PCARE	ENST00000602958.1	TSL:4	n.-129A>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.985

AC:

149840

AN:

152152

Hom.:

73818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.948

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.993

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.988

GnomAD4 exome

AF:

1.00

AC:

154

AN:

154

Hom.:

Cov.:

AF XY:

1.00

AC XY:

106

AN XY:

106

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

132

AN:

132

Other (OTH)

AF:

1.00

AC:

AN:

GnomAD4 genome

AF:

0.985

AC:

149951

AN:

152270

Hom.:

73869

Cov.:

AF XY:

0.985

AC XY:

73354

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.948

AC:

39378

AN:

41538

American (AMR)

AF:

0.993

AC:

15204

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5159

AN:

5160

South Asian (SAS)

AF:

0.999

AC:

4820

AN:

4824

European-Finnish (FIN)

AF:

1.00

AC:

10618

AN:

10618

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68006

AN:

68032

Other (OTH)

AF:

0.988

AC:

2089

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

198

298

397

496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.992

Hom.:

8869

Bravo

AF:

0.983

Asia WGS

AF:

0.994

AC:

3456

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.41

(source)

DANN

Benign

0.38

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over