rs398053355

Positions:

• chr1-113116443-ACT-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_014813.3(LRIG2):​c.2680+10_2680+11del 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 NM_014813.3 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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LRIG2	NM_014813.3	c.2680+10_2680+11del		splice_region_variant, intron_variant		ENST00000361127.6	NP_055628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRIG2	ENST00000361127.6	c.2680+10_2680+11del		splice_region_variant, intron_variant		1	NM_014813.3	ENSP00000355396	P1
LRIG2	ENST00000466161.1	n.1952+10_1952+11del		splice_region_variant, intron_variant, non_coding_transcript_variant		2
LRIG2	ENST00000492207.5	n.1459+10_1459+11del		splice_region_variant, intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.839 AC: 201585 AN: 240184 Hom.: 85353 AF XY: 0.848 AC XY: 109983 AN XY: 129684

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 SAS exome AF: 0.894

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

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.883

Gnomad4 EAS exome AF: 0.959

Gnomad4 SAS exome AF: 0.895

Gnomad4 FIN exome AF: 0.883

Gnomad4 NFE exome AF: 0.842

Gnomad4 OTH exome AF: 0.838

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

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.880

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.793

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 21, 2022

- -

Computational scores

Source: dbNSFP v4.3

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;