1-113091334-C-G

Variant names:

• chr1-113091334-C-G
• rs554758747
• NM_014813.3:c.256C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001312686.2(LRIG2):​c.-166C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,000 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: LRIG2 NM_001312686.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Ochoa syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001312686.2. 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.256C>G	p.Arg86Gly	missense	Exon 2 of 18	NP_055628.1	O94898
	LRIG2	NM_001312686.2		c.-166C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 19	NP_001299615.1
	LRIG2	NM_001312686.2		c.-166C>G		5_prime_UTR	Exon 2 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.256C>G	p.Arg86Gly	missense	Exon 2 of 18	ENSP00000355396.4	O94898
	LRIG2	ENST00000922864.1		c.256C>G	p.Arg86Gly	missense	Exon 2 of 19	ENSP00000592923.1
	LRIG2	ENST00000922865.1		c.256C>G	p.Arg86Gly	missense	Exon 2 of 18	ENSP00000592924.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152000 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152000 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74234

African (AFR) AF: 0.00 AC: 0 AN: 41378

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.097
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.3
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.11
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.026	D
Polyphen		0.17	B
Vest4		0.54
MutPred		0.73		Loss of stability (P = 0.0436)
MVP		0.79
MPC		0.23
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.22
gMVP		0.46
Mutation Taster		=63/37	polymorphism

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: rs554758747; hg19: chr1-113633956;