rs398053355

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 ENST00000361127.6(LRIG2):​c.2680+8_2680+9delCT variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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 ENST00000361127.6 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24

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]

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 id is 260443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-113116443-ACT-A is described in Lovd as [Benign].
• 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

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

Gnomad4 AFR exome AF: 0.584 AC: 19127 AN: 32758

Gnomad4 AMR exome AF: 0.783 AC: 33113 AN: 42270

Gnomad4 ASJ exome AF: 0.883 AC: 22551 AN: 25532

Gnomad4 EAS exome AF: 0.959 AC: 37042 AN: 38620

Gnomad4 SAS exome AF: 0.895 AC: 74231 AN: 82978

Gnomad4 FIN exome AF: 0.883 AC: 46921 AN: 53142

Gnomad4 NFE exome AF: 0.842 AC: 921250 AN: 1094122

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.592 AC: 0.591703 AN: 0.591703

Gnomad4 AMR AF: 0.782 AC: 0.782113 AN: 0.782113

Gnomad4 ASJ AF: 0.880 AC: 0.879896 AN: 0.879896

Gnomad4 EAS AF: 0.940 AC: 0.940495 AN: 0.940495

Gnomad4 SAS AF: 0.911 AC: 0.910507 AN: 0.910507

Gnomad4 FIN AF: 0.882 AC: 0.882192 AN: 0.882192

Gnomad4 NFE AF: 0.841 AC: 0.841492 AN: 0.841492

Gnomad4 OTH AF: 0.793 AC: 0.792694 AN: 0.792694

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs398053355; hg19: chr1-113659065; COSMIC: COSV63160865;