9-28476134-A-T

Position:

• chr9-28476134-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.-313-109T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,568 control chromosomes in the GnomAD database, including 61,361 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 0.89 (61215 hom., cov: 33)
  • Exomes 𝑓: 0.96 (146 hom.)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-313-109T>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.-313-109T>A		intron_variant			NM_001258282.3	ENSP00000513694	P1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136086 AN: 152130 Hom.: 61167 Cov.: 33

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.884

GnomAD4 exome AF: 0.956 AC: 306 AN: 320 Hom.: 146 AF XY: 0.963 AC XY: 183 AN XY: 190

Gnomad4 FIN exome AF: 0.955

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.895 AC: 136191 AN: 152248 Hom.: 61215 Cov.: 33 AF XY: 0.899 AC XY: 66918 AN XY: 74442

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.915

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.973

Gnomad4 FIN AF: 0.965

Gnomad4 NFE AF: 0.922

Gnomad4 OTH AF: 0.884

Alfa AF: 0.901 Hom.: 7712

Bravo AF: 0.885

Asia WGS AF: 0.973 AC: 3380 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.98
DANN	Benign	0.48

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: rs2026376; hg19: chr9-28476132;