chr9-27950865-G-T

Variant names:

• chr9-27950865-G-T
• rs10757699
• NM_001258282.3:c.-35-159C>A

Variant summary

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

The NM_152570.4(LINGO2):​c.-35-159C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,024 control chromosomes in the GnomAD database, including 23,861 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 0.54 (23861 hom., cov: 32)
• Consequence: LINGO2 NM_152570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152570.4. 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.-35-159C>A		intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-35-159C>A		intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-35-159C>A		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.-35-159C>A		intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.-35-159C>A		intron	N/A	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.-35-159C>A		intron	N/A	ENSP00000513695.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81609 AN: 151904 Hom.: 23861 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.537 AC: 81628 AN: 152024 Hom.: 23861 Cov.: 32 AF XY: 0.546 AC XY: 40552 AN XY: 74330

African (AFR) AF: 0.301 AC: 12470 AN: 41440

American (AMR) AF: 0.547 AC: 8357 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2047 AN: 3472

East Asian (EAS) AF: 0.799 AC: 4127 AN: 5166

South Asian (SAS) AF: 0.585 AC: 2814 AN: 4814

European-Finnish (FIN) AF: 0.762 AC: 8044 AN: 10562

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41846 AN: 67966

Other (OTH) AF: 0.541 AC: 1144 AN: 2116

Alfa AF: 0.589 Hom.: 110570

Bravo AF: 0.516

Asia WGS AF: 0.633 AC: 2201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.59
PhyloP100		-1.0
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: rs10757699; hg19: chr9-27950863;