rs17506843

chr9-27949152-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001258282.3(LINGO2):c.1520G>A(p.Arg507His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: LINGO2 NM_001258282.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49

Genes affected

LINGO2 (HGNC:21207): (leucine rich repeat and Ig domain containing 2) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.091401875).
• BS2: High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.1520G>A	p.Arg507His	missense_variant	7/7	ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.1520G>A	p.Arg507His	missense_variant	7/7		NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152120 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: 0.000118

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000836 AC: 21 AN: 251310 Hom.: 0 AF XY: 0.0000810 AC XY: 11 AN XY: 135808

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000128 AC: 187 AN: 1461774 Hom.: 0 Cov.: 33 AF XY: 0.000129 AC XY: 94 AN XY: 727186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74304

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000166 Hom.: 0

Bravo AF: 0.0000831

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000824 AC: 10

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.040	T;T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.88	N;N;.
REVEL	Benign	0.045
Sift	Benign	0.32	T;T;.
Sift4G	Benign	0.27	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.21
MVP		0.15
MPC		0.19
ClinPred		0.034	T
GERP RS		5.8
Varity_R		0.098
gMVP		0.41

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: rs17506843; hg19: chr9-27949150; COSMIC: COSV58057030; COSMIC: COSV58057030;