3-101222848-A-C

Variant names:

• chr3-101222848-A-C
• rs813449
• NM_016247.4:c.*4121T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016247.4(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 NM_016247.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.59
• Publications: 3 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: Benign. The variant received -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 VariationId 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.

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.*4121T>G		3_prime_UTR	Exon 19 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.*4121T>G		3_prime_UTR	Exon 19 of 19	ENSP00000193391.6	Q9BZV3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.602 AC: 24948 AN: 41474

American (AMR) AF: 0.691 AC: 10556 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1816 AN: 3466

East Asian (EAS) AF: 0.636 AC: 3293 AN: 5178

South Asian (SAS) AF: 0.588 AC: 2840 AN: 4828

European-Finnish (FIN) AF: 0.739 AC: 7803 AN: 10560

Middle Eastern (MID) AF: 0.559 AC: 162 AN: 290

European-Non Finnish (NFE) AF: 0.654 AC: 44466 AN: 67982

Other (OTH) AF: 0.621 AC: 1311 AN: 2110

Alfa AF: 0.649 Hom.: 4015

Bravo AF: 0.635

Asia WGS AF: 0.625 AC: 2172 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.64
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs813449; hg19: chr3-100941692;