rs6688685

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-113093538-A-G
• chr1-113093538-A-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_014813.3(LRIG2):​c.489A>G​(p.Ser163Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00844 in 1,584,488 control chromosomes in the GnomAD database, including 1,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.046 (524 hom., cov: 31)
  • Exomes 𝑓: 0.0046 (482 hom.)
• Consequence: LRIG2 NM_014813.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.330
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 1-113093538-A-G is Benign according to our data. Variant chr1-113093538-A-G is described in ClinVar as Benign. ClinVar VariationId is 3344535.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6799 AN: 147884 Hom.: 520 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00127

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.000534

Gnomad OTH AF: 0.0280

GnomAD2 exomes AF: 0.0118 AC: 2958 AN: 251282 AF XY: 0.00845

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.00868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00571

GnomAD4 exome AF: 0.00456 AC: 6550 AN: 1436500 Hom.: 482 Cov.: 31 AF XY: 0.00385 AC XY: 2752 AN XY: 714432

African (AFR) AF: 0.159 AC: 5228 AN: 32946

American (AMR) AF: 0.00999 AC: 439 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.0000793 AC: 2 AN: 25220

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

South Asian (SAS) AF: 0.000407 AC: 35 AN: 86026

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

Middle Eastern (MID) AF: 0.00607 AC: 34 AN: 5602

European-Non Finnish (NFE) AF: 0.000163 AC: 179 AN: 1095472

Other (OTH) AF: 0.0108 AC: 633 AN: 58810

GnomAD4 genome AF: 0.0461 AC: 6826 AN: 147988 Hom.: 524 Cov.: 31 AF XY: 0.0448 AC XY: 3218 AN XY: 71756

African (AFR) AF: 0.160 AC: 6465 AN: 40400

American (AMR) AF: 0.0181 AC: 258 AN: 14244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 4936

South Asian (SAS) AF: 0.00128 AC: 6 AN: 4702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9556

Middle Eastern (MID) AF: 0.0140 AC: 4 AN: 286

European-Non Finnish (NFE) AF: 0.000534 AC: 36 AN: 67462

Other (OTH) AF: 0.0277 AC: 57 AN: 2058

Alfa AF: 0.0171 Hom.: 560

Bravo AF: 0.0515

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	LRIG2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.3
DANN	Benign	0.76
PhyloP100		0.33
Mutation Taster		=92/8	polymorphism (auto)

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;