9-28372708-C-T

Variant names:

• chr9-28372708-C-T
• rs1331870
• NM_001258282.3:c.-195+128G>A

Variant summary

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

The NM_001258282.3(LINGO2):​c.-195+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 152,730 control chromosomes in the GnomAD database, including 75,696 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 1.0 (75491 hom., cov: 33)
  • Exomes 𝑓: 1.0 (205 hom.)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.-195+128G>A		intron	N/A	NP_001245211.1	Q7L985
	LINGO2	NM_001354574.2		c.-194-77342G>A		intron	N/A	NP_001341503.1	Q7L985
	LINGO2	NM_001354575.2		c.-195+128G>A		intron	N/A	NP_001341504.1	Q7L985

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-195+128G>A		intron	N/A	ENSP00000513694.1	Q7L985
	LINGO2	ENST00000379992.6	TSL:5	c.-246+128G>A		intron	N/A	ENSP00000369328.1	Q7L985
	LINGO2	ENST00000698400.1		c.-410+128G>A		intron	N/A	ENSP00000513695.1	Q7L985

Frequencies

GnomAD3 genomes AF: 0.996 AC: 151532 AN: 152202 Hom.: 75436 Cov.: 33

Gnomad AFR AF: 0.985

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.997

GnomAD4 exome AF: 1.00 AC: 410 AN: 410 Hom.: 205 AF XY: 1.00 AC XY: 248 AN XY: 248

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 404 AN: 404

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.996 AC: 151645 AN: 152320 Hom.: 75491 Cov.: 33 AF XY: 0.996 AC XY: 74160 AN XY: 74470

African (AFR) AF: 0.985 AC: 40925 AN: 41568

American (AMR) AF: 0.998 AC: 15276 AN: 15300

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

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 1.00 AC: 4826 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68030 AN: 68032

Other (OTH) AF: 0.997 AC: 2110 AN: 2116

Alfa AF: 0.997 Hom.: 9209

Bravo AF: 0.995

Asia WGS AF: 0.997 AC: 3452 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.22
PhyloP100		-0.062
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: rs1331870; hg19: chr9-28372706;