9-28509553-T-G

Variant names:

• chr9-28509553-T-G
• rs6476077
• NM_001258282.3:c.-313-33528A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):​c.-313-33528A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 152,288 control chromosomes in the GnomAD database, including 71,039 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.96 (71039 hom., cov: 33)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.-313-33528A>C		intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-280-33528A>C		intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-313-33528A>C		intron	N/A	NP_001341504.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-313-33528A>C		intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.-364-33528A>C		intron	N/A	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.-528-33528A>C		intron	N/A	ENSP00000513695.1

Frequencies

GnomAD3 genomes AF: 0.965 AC: 146848 AN: 152170 Hom.: 71011 Cov.: 33

Gnomad AFR AF: 0.910

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.986

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.973

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.965 AC: 146928 AN: 152288 Hom.: 71039 Cov.: 33 AF XY: 0.963 AC XY: 71699 AN XY: 74442

African (AFR) AF: 0.910 AC: 37816 AN: 41564

American (AMR) AF: 0.986 AC: 15072 AN: 15292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3471 AN: 3472

East Asian (EAS) AF: 0.878 AC: 4540 AN: 5168

South Asian (SAS) AF: 0.945 AC: 4562 AN: 4828

European-Finnish (FIN) AF: 0.977 AC: 10357 AN: 10598

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67851 AN: 68044

Other (OTH) AF: 0.972 AC: 2057 AN: 2116

Alfa AF: 0.972 Hom.: 3909

Bravo AF: 0.963

Asia WGS AF: 0.920 AC: 3200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.55
PhyloP100		0.15
Mutation Taster		=100/0	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: rs6476077; hg19: chr9-28509551;