3-101232784-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate

The NM_016247.4(IMPG2):​c.3230G>C​(p.Cys1077Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. C1077F) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

IMPG2
NM_016247.4 missense

Scores

13
5
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
IMPG2 (HGNC:18362): (interphotoreceptor matrix proteoglycan 2) The protein encoded by this gene binds chondroitin sulfate and hyaluronan and is a proteoglycan. The encoded protein plays a role in the organization of the interphotoreceptor matrix and may promote the growth and maintenance of the light-sensitive photoreceptor outer segment. Defects in this gene are a cause of retinitis pigmentosa type 56 and maculopathy, IMPG2-related.[provided by RefSeq, Mar 2011]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr3-101232784-C-A is described in Lovd as [Likely_pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IMPG2NM_016247.4 linkc.3230G>C p.Cys1077Ser missense_variant Exon 15 of 19 ENST00000193391.8 NP_057331.2 Q9BZV3F1T0J3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IMPG2ENST00000193391.8 linkc.3230G>C p.Cys1077Ser missense_variant Exon 15 of 19 1 NM_016247.4 ENSP00000193391.6 Q9BZV3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461698
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727160
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.27
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.63
D
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.93
D
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.94
D
MetaSVM
Uncertain
0.14
D
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-8.9
D
REVEL
Pathogenic
0.78
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.98
MutPred
0.76
Gain of MoRF binding (P = 0.1072);
MVP
0.65
MPC
0.46
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.91
gMVP
0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-100951628; API