3-101222848-A-C

Position:

• chr3-101222848-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000193391.8(IMPG2):​c.*4121T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,082 control chromosomes in the GnomAD database, including 31,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31615 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IMPG2 ENST00000193391.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.59

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-101222848-A-C is Benign according to our data. Variant chr3-101222848-A-C is described in ClinVar as [Benign]. Clinvar id is 342272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPG2	NM_016247.4	c.*4121T>G		3_prime_UTR_variant	19/19	ENST00000193391.8	NP_057331.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPG2	ENST00000193391.8	c.*4121T>G		3_prime_UTR_variant	19/19	1	NM_016247.4	ENSP00000193391	P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97593 AN: 151962 Hom.: 31578 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.618

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.642 AC: 97668 AN: 152082 Hom.: 31615 Cov.: 32 AF XY: 0.645 AC XY: 47927 AN XY: 74340

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.621

Alfa AF: 0.649 Hom.: 4015

Bravo AF: 0.635

Asia WGS AF: 0.625 AC: 2172 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs813449; hg19: chr3-100941692;