9-28371752-A-C

Position:

• chr9-28371752-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):​c.-195+1084T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,128 control chromosomes in the GnomAD database, including 47,983 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 0.78 (47983 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-195+1084T>G		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-195+1084T>G		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119157 AN: 152010 Hom.: 47938 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.784 AC: 119260 AN: 152128 Hom.: 47983 Cov.: 32 AF XY: 0.786 AC XY: 58429 AN XY: 74380

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.874

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.827

Alfa AF: 0.777 Hom.: 2545

Bravo AF: 0.777

Asia WGS AF: 0.823 AC: 2863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.34

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: rs1331866; hg19: chr9-28371750; COSMIC: COSV66149550;