9-28476134-A-T

Variant names:

• chr9-28476134-A-T
• rs2026376
• NM_001258282.3:c.-313-109T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-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 rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-313-109T>A		intron_variant	Intron 3 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-313-109T>A		intron_variant	Intron 3 of 6		NM_001258282.3	ENSP00000513694.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.955 AC: 300 AN: 314

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

African (AFR) AF: 0.802 AC: 33294 AN: 41520

American (AMR) AF: 0.915 AC: 14001 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3052 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5176

South Asian (SAS) AF: 0.973 AC: 4698 AN: 4828

European-Finnish (FIN) AF: 0.965 AC: 10235 AN: 10604

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62737 AN: 68028

Other (OTH) AF: 0.884 AC: 1868 AN: 2114

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
PhyloP100		-0.54
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: rs2026376; hg19: chr9-28476132;