1-113100266-GA-GAA

Variant names:

• chr1-113100266-G-GA
• rs587776945
• NM_014813.3:c.1230dupA

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_014813.3(LRIG2):​c.1230dupA​(p.Ser411IlefsTer3) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRIG2 NM_014813.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51
• Publications: 2 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Ochoa syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000303525 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 10 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014813.3. 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
	LRIG2	NM_014813.3	MANE Select	c.1230dupA	p.Ser411IlefsTer3	frameshift	Exon 10 of 18	NP_055628.1	O94898
	LRIG2	NM_001312686.2		c.921dupA	p.Ser308IlefsTer3	frameshift	Exon 11 of 19	NP_001299615.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRIG2	ENST00000361127.6	TSL:1 MANE Select	c.1230dupA	p.Ser411IlefsTer3	frameshift	Exon 10 of 18	ENSP00000355396.4	O94898
	LRIG2	ENST00000922864.1		c.1230dupA	p.Ser411IlefsTer3	frameshift	Exon 10 of 19	ENSP00000592923.1
	LRIG2	ENST00000890456.1		c.1164dupA	p.Ser389IlefsTer3	frameshift	Exon 9 of 17	ENSP00000560515.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs587776945;

hg19: chr1-113642888;