Genetic Variant PCARE:c.*2929T>C (chr2-29061940-A-G) – 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.*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

Clinical Significance

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

Conservation

PhyloP100: -0.498

Publications

5 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=-0.94).

BP6

Variant 2-29061940-A-G is Benign according to our data. Variant chr2-29061940-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

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.*2929T>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.*2929T>C		3_prime_UTR	Exon 2 of 2	ENSP00000332809.4	A6NGG8
	PCARE	ENST00000602958.1	TSL:4	n.216T>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.936

AC:

142308

AN:

152110

Hom.:

67326

Cov.:

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:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.935

AC:

142386

AN:

152228

Hom.:

67351

Cov.:

AF XY:

0.937

AC XY:

69761

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.775

AC:

32164

AN:

41488

American (AMR)

AF:

0.978

AC:

14960

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.996

AC:

3457

AN:

3472

East Asian (EAS)

AF:

0.997

AC:

5159

AN:

5172

South Asian (SAS)

AF:

0.999

AC:

4818

AN:

4822

European-Finnish (FIN)

AF:

1.00

AC:

10620

AN:

10620

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67970

AN:

68040

Other (OTH)

AF:

0.963

AC:

2035

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

386

772

1158

1544

1930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<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:

0.904

Hom.:

18346

Bravo

AF:

0.927

Asia WGS

AF:

0.979

AC:

3406

AN:

3478

ClinVar

ClinVar submissions as Germline

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

-0.94

CADD

Benign

3.1

(source)

DANN

Benign

0.54

PhyloP100

-0.50

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over