3-101223189-A-T

Position:

• chr3-101223189-A-T

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.*3780T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,206 control chromosomes in the GnomAD database, including 48,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48814 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: IMPG2 ENST00000193391.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.115

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=-0.84).
• BP6: Variant 3-101223189-A-T is Benign according to our data. Variant chr3-101223189-A-T is described in ClinVar as [Benign]. Clinvar id is 342277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPG2	NM_016247.4	c.*3780T>A		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.*3780T>A		3_prime_UTR_variant	19/19	1	NM_016247.4	ENSP00000193391	P1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121754 AN: 152086 Hom.: 48756 Cov.: 33

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.782

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.801 AC: 121865 AN: 152204 Hom.: 48814 Cov.: 33 AF XY: 0.802 AC XY: 59681 AN XY: 74402

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.784

Alfa AF: 0.801 Hom.: 6052

Bravo AF: 0.798

Asia WGS AF: 0.822 AC: 2859 AN: 3476

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	-0.84
CADD	Benign	5.3
DANN	Benign	0.75

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: rs511575; hg19: chr3-100942033;