rs587776945

Positions:

• chr1-113100266-GA-G
• chr1-113100266-GA-GAA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The ENST00000361127.6(LRIG2):​c.1230del​(p.Glu410AspfsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRIG2 ENST00000361127.6 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.51

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-113100266-GA-G is Pathogenic according to our data. Variant chr1-113100266-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 40206.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRIG2	NM_014813.3	c.1230del	p.Glu410AspfsTer6	frameshift_variant	10/18	ENST00000361127.6	NP_055628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRIG2	ENST00000361127.6	c.1230del	p.Glu410AspfsTer6	frameshift_variant	10/18	1	NM_014813.3	ENSP00000355396	P1
LRIG2	ENST00000466069.5	n.121del		non_coding_transcript_exon_variant	2/5	2
LRIG2	ENST00000470000.1	n.58del		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Urofacial syndrome 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 07, 2013

- -

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: rs587776945; hg19: chr1-113642888;