9-28869371-G-C

Position:

• chr9-28869371-G-C

Variant summary

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

The NM_001258282.3(LINGO2):​c.-395+78447C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,920 control chromosomes in the GnomAD database, including 6,424 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 0.21 (6424 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-395+78447C>G		intron_variant		ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-395+78447C>G		intron_variant			NM_001258282.3	ENSP00000513694.1
LINGO2	ENST00000698401.1	c.-765+78447C>G		intron_variant				ENSP00000513696.1
LINGO2	ENST00000698402.1	c.-550+78447C>G		intron_variant				ENSP00000513697.1
LINGO2	ENST00000698404.1	c.-506+78447C>G		intron_variant				ENSP00000513699.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32038 AN: 151802 Hom.: 6407 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.211 AC: 32099 AN: 151920 Hom.: 6424 Cov.: 31 AF XY: 0.209 AC XY: 15502 AN XY: 74240

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0966

Gnomad4 FIN AF: 0.0980

Gnomad4 NFE AF: 0.0792

Gnomad4 OTH AF: 0.171

Alfa AF: 0.165 Hom.: 536

Bravo AF: 0.228

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.5
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3849874; hg19: chr9-28869369;