rs766305807

Variant names:

• chr3-101304267-C-G
• rs766305807
• NM_016247.4:c.380G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-101304267-C-G
• chr3-101304267-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Moderate PP5_Moderate

The NM_016247.4(IMPG2):​c.380G>C​(p.Arg127Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R127Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IMPG2 NM_016247.4 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 5.74
• Publications: 4 publications found

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):

• IMPG2-related recessive retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 56

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• vitelliform macular dystrophy 5

  Inheritance: Unknown, AD Classification: DEFINITIVE, LIMITED 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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885
• PP5: Variant 3-101304267-C-G is Pathogenic according to our data. Variant chr3-101304267-C-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 191182.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016247.4. 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
	IMPG2	NM_016247.4	MANE Select	c.380G>C	p.Arg127Pro	missense	Exon 3 of 19	NP_057331.2	Q9BZV3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPG2	ENST00000193391.8	TSL:1 MANE Select	c.380G>C	p.Arg127Pro	missense	Exon 3 of 19	ENSP00000193391.6	Q9BZV3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)
1	-	-	Vitelliform macular dystrophy 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		5.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.62		Loss of MoRF binding (P = 0.0345)
MVP		0.65
MPC		0.49
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.91
gMVP		0.86
Mutation Taster		=68/32	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs766305807; hg19: chr3-101023111;