9-28677726-A-T

Position:

• chr9-28677726-A-T

Variant summary

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

The NM_001258282.3(LINGO2):​c.-394-7446T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,162 control chromosomes in the GnomAD database, including 934 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 0.097 (934 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-394-7446T>A		intron_variant		ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-394-7446T>A		intron_variant			NM_001258282.3	ENSP00000513694.1
LINGO2	ENST00000698401.1	c.-764-7446T>A		intron_variant				ENSP00000513696.1
LINGO2	ENST00000698402.1	c.-549-7446T>A		intron_variant				ENSP00000513697.1
LINGO2	ENST00000698404.1	c.-505-7446T>A		intron_variant				ENSP00000513699.1

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14777 AN: 152046 Hom.: 935 Cov.: 31

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0925

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0853

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

GnomAD4 genome AF: 0.0971 AC: 14771 AN: 152162 Hom.: 934 Cov.: 31 AF XY: 0.101 AC XY: 7524 AN XY: 74378

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.0923

Gnomad4 ASJ AF: 0.0424

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.0844

Alfa AF: 0.0592 Hom.: 72

Bravo AF: 0.0868

Asia WGS AF: 0.140 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.1
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10968712; hg19: chr9-28677724;