9-28644925-A-G

Variant names:

• chr9-28644925-A-G
• rs10511830
• NM_001258282.3:c.-314+25275T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):​c.-314+25275T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 152,080 control chromosomes in the GnomAD database, including 876 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 0.090 (876 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• 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]

LOC105376003 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-314+25275T>C		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.-314+25275T>C		intron_variant	Intron 3 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.0899 AC: 13657 AN: 151962 Hom.: 868 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0744

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0588

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0900 AC: 13684 AN: 152080 Hom.: 876 Cov.: 32 AF XY: 0.0935 AC XY: 6950 AN XY: 74346

African (AFR) AF: 0.0989 AC: 4108 AN: 41520

American (AMR) AF: 0.223 AC: 3393 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3470

East Asian (EAS) AF: 0.0745 AC: 386 AN: 5178

South Asian (SAS) AF: 0.0978 AC: 472 AN: 4826

European-Finnish (FIN) AF: 0.0858 AC: 909 AN: 10596

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0587 AC: 3991 AN: 67940

Other (OTH) AF: 0.0799 AC: 169 AN: 2114

Alfa AF: 0.0693 Hom.: 241

Bravo AF: 0.103

Asia WGS AF: 0.130 AC: 450 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.16
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: rs10511830; hg19: chr9-28644923;