rs111784356

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_016247.4(IMPG2):c.3439C>T(p.Pro1147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00358 in 1,613,846 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1147R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.019 ( 83 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 83 hom. )

Consequence

IMPG2
NM_016247.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 0.940

Publications

5 publications found

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]

IMPG2 Gene-Disease associations (from GenCC):

vitelliform macular dystrophy 5
Inheritance: AD, Unknown Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
inherited retinal dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa 56
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
adult-onset foveomacular vitelliform dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IMPG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016234517).

BP6

Variant 3-101229574-G-A is Benign according to our data. Variant chr3-101229574-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 191179.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPG2	NM_016247.4 link	c.3439C>T	p.Pro1147Ser	missense_variant	Exon 17 of 19	ENST00000193391.8	NP_057331.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPG2	ENST00000193391.8 link	c.3439C>T	p.Pro1147Ser	missense_variant	Exon 17 of 19	1	NM_016247.4	ENSP00000193391.6

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2800

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0643

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00509

AC:

1276

AN:

250866

AF XY:

0.00353

show subpopulations

Gnomad AFR exome

AF:

0.0674

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00202

AC:

2955

AN:

1461566

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1224

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.0686

AC:

2295

AN:

33458

American (AMR)

AF:

0.00434

AC:

194

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000139

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00439

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.000130

AC:

144

AN:

1111886

Other (OTH)

AF:

0.00472

AC:

285

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

149

298

447

596

745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.0186

AC:

2825

AN:

152280

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1343

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0647

AC:

2687

AN:

41550

American (AMR)

AF:

0.00621

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68030

Other (OTH)

AF:

0.0123

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

132

264

396

528

660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00619

Hom.:

Bravo

AF:

0.0217

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0645

AC:

284

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00606

AC:

736

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Retinitis pigmentosa

Uncertain:1Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

May 28, 2019

Mendelics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Sep 28, 2016

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.023

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

0.94

PrimateAI

Benign

0.23

PROVEAN

Benign

-2.0

REVEL

Benign

0.095

Sift

Benign

0.088

Sift4G

Benign

0.85

Polyphen

0.011

Vest4

0.13

MVP

0.17

MPC

0.071

ClinPred

0.0034

GERP RS

1.2

Varity_R

0.048

gMVP

0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over