1-113093538-A-C

Variant names:

• chr1-113093538-A-C
• rs6688685
• NM_014813.3:c.489A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014813.3(LRIG2):​c.489A>C​(p.Ser163Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S163S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LRIG2 NM_014813.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• 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

ENSG00000303525 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.33 with no splicing effect.

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.489A>C	p.Ser163Ser	synonymous	Exon 4 of 18	NP_055628.1	O94898
	LRIG2	NM_001312686.2		c.180A>C	p.Ser60Ser	synonymous	Exon 5 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.489A>C	p.Ser163Ser	synonymous	Exon 4 of 18	ENSP00000355396.4	O94898
	LRIG2	ENST00000922864.1		c.489A>C	p.Ser163Ser	synonymous	Exon 4 of 19	ENSP00000592923.1
	LRIG2	ENST00000890456.1		c.423A>C	p.Ser141Ser	synonymous	Exon 3 of 17	ENSP00000560515.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436546 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 714458

African (AFR) AF: 0.00 AC: 0 AN: 32992

American (AMR) AF: 0.00 AC: 0 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25220

East Asian (EAS) AF: 0.00 AC: 0 AN: 37706

South Asian (SAS) AF: 0.00 AC: 0 AN: 86026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5602

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095472

Other (OTH) AF: 0.00 AC: 0 AN: 58810

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.9
DANN	Benign	0.76
PhyloP100		0.33
Mutation Taster		=92/8	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: rs6688685; hg19: chr1-113636160;