2-29073661-T-C

Variant names:

• chr2-29073661-T-C
• rs267606690
• NM_001029883.3:c.601A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001029883.3(PCARE):​c.601A>G​(p.Ile201Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I201F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCARE NM_001029883.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 7 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

ENSG00000308575 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09570843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCARE	NM_001029883.3	c.601A>G	p.Ile201Val	missense_variant	Exon 1 of 2	ENST00000331664.6	NP_001025054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCARE	ENST00000331664.6	c.601A>G	p.Ile201Val	missense_variant	Exon 1 of 2	2	NM_001029883.3	ENSP00000332809.4
ENSG00000308575	ENST00000835145.1	n.224+4494T>C		intron_variant	Intron 2 of 2
ENSG00000308575	ENST00000835146.1	n.207+4494T>C		intron_variant	Intron 2 of 2
ENSG00000308575	ENST00000835147.1	n.171+4494T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249574 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.5
DANN	Benign	0.86
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.31
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.034
Sift	Benign	0.12	T
Sift4G	Benign	0.22	T
Polyphen		0.31	B
Vest4		0.10
MutPred		0.18		Loss of methylation at K197 (P = 0.1179);
MVP		0.27
MPC		0.016
ClinPred		0.076	T
GERP RS		-3.1
Varity_R		0.040
gMVP		0.12
Mutation Taster		=99/1	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: rs267606690; hg19: chr2-29296527;