1-113116443-ACT-A

Variant names:

• chr1-113116443-ACT-A
• rs398053355
• NM_014813.3:c.2680+10_2680+11delCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_014813.3(LRIG2):​c.2680+10_2680+11delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 1,586,146 control chromosomes in the GnomAD database, including 558,203 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46745 hom., cov: 0)
  • Exomes 𝑓: 0.84 (511458 hom.)
• Consequence: LRIG2 NM_014813.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24
• Publications: 1 publications found

Genes affected

LRIG2 (HGNC:20889): (leucine rich repeats and immunoglobulin like domains 2) This gene encodes a transmembrane protein containing leucine-rich repeats and immunoglobulin-like domains. The encoded protein promotes epidermal growth factor signalling, resulting in increased proliferation. Its expression in the cytoplasm of glioma cells is correlated with poor survival. Mutations in this gene can cause urofacial syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

LRIG2 Gene-Disease associations (from GenCC):

• urofacial syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Ochoa syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000303525 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-113116443-ACT-A is Benign according to our data. Variant chr1-113116443-ACT-A is described in ClinVar as Benign. ClinVar VariationId is 260443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRIG2	NM_014813.3	c.2680+10_2680+11delCT		intron_variant	Intron 16 of 17	ENST00000361127.6	NP_055628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRIG2	ENST00000361127.6	c.2680+8_2680+9delCT		splice_region_variant, intron_variant	Intron 16 of 17	1	NM_014813.3	ENSP00000355396.4
LRIG2	ENST00000466161.1	n.1952+8_1952+9delCT		splice_region_variant, intron_variant	Intron 6 of 7	2
LRIG2	ENST00000492207.5	n.1459+8_1459+9delCT		splice_region_variant, intron_variant	Intron 6 of 7	5
ENSG00000303525	ENST00000795269.1	n.363+13312_363+13313delAG		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117832 AN: 151786 Hom.: 46735 Cov.: 0

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.790

GnomAD2 exomes AF: 0.839 AC: 201585 AN: 240184 AF XY: 0.848

Gnomad AFR exome AF: 0.588

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.883

Gnomad EAS exome AF: 0.945

Gnomad FIN exome AF: 0.881

Gnomad NFE exome AF: 0.848

Gnomad OTH exome AF: 0.848

GnomAD4 exome AF: 0.843 AC: 1208676 AN: 1434242 Hom.: 511458 AF XY: 0.846 AC XY: 600608 AN XY: 710096

African (AFR) AF: 0.584 AC: 19127 AN: 32758

American (AMR) AF: 0.783 AC: 33113 AN: 42270

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 22551 AN: 25532

East Asian (EAS) AF: 0.959 AC: 37042 AN: 38620

South Asian (SAS) AF: 0.895 AC: 74231 AN: 82978

European-Finnish (FIN) AF: 0.883 AC: 46921 AN: 53142

Middle Eastern (MID) AF: 0.859 AC: 4860 AN: 5656

European-Non Finnish (NFE) AF: 0.842 AC: 921250 AN: 1094122

Other (OTH) AF: 0.838 AC: 49581 AN: 59164

GnomAD4 genome AF: 0.776 AC: 117876 AN: 151904 Hom.: 46745 Cov.: 0 AF XY: 0.780 AC XY: 57916 AN XY: 74284

African (AFR) AF: 0.592 AC: 24461 AN: 41340

American (AMR) AF: 0.782 AC: 11946 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3055 AN: 3472

East Asian (EAS) AF: 0.940 AC: 4868 AN: 5176

South Asian (SAS) AF: 0.911 AC: 4385 AN: 4816

European-Finnish (FIN) AF: 0.882 AC: 9323 AN: 10568

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57176 AN: 67946

Other (OTH) AF: 0.793 AC: 1671 AN: 2108

Alfa AF: 0.823 Hom.: 9402

Bravo AF: 0.761

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Apr 21, 2022

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
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: rs398053355; hg19: chr1-113659065; COSMIC: COSV63160865;