rs786205565

Variant names:

• chr3-101319817-G-C
• rs786205565
• NM_016247.4:c.101C>G

Variant summary

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

The NM_016247.4(IMPG2):​c.101C>G​(p.Ser34Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IMPG2 NM_016247.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 4.42
• Publications: 1 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):

• 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

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=0.20217356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPG2	NM_016247.4	c.101C>G	p.Ser34Cys	missense_variant	Exon 2 of 19	ENST00000193391.8	NP_057331.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPG2	ENST00000193391.8	c.101C>G	p.Ser34Cys	missense_variant	Exon 2 of 19	1	NM_016247.4	ENSP00000193391.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

-

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

Significance: Likely pathogenic

Review Status: flagged submission

Collection Method: research

- -

Vitelliform macular dystrophy 5 Uncertain:1

Mar 14, 2024

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

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.054	T
Eigen	Benign	0.0033
Eigen_PC	Benign	0.031
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.081
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.073	T
Polyphen		0.97	D
Vest4		0.45
MutPred		0.34		Loss of disorder (P = 0.0136);
MVP		0.27
MPC		0.22
ClinPred		0.66	D
GERP RS		4.8
Varity_R		0.13
gMVP		0.52
Mutation Taster		=95/5	disease causing (ClinVar)

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: rs786205565; hg19: chr3-101038661;