chr9-28366645-G-A

Position:

• chr9-28366645-G-A

Variant summary

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

The NM_001258282.3(LINGO2):​c.-195+6191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 149,842 control chromosomes in the GnomAD database, including 1,170 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 0.12 (1170 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-195+6191C>T		intron_variant		ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-195+6191C>T		intron_variant			NM_001258282.3	ENSP00000513694	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17592 AN: 149738 Hom.: 1170 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0453

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.0784

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.117 AC: 17596 AN: 149842 Hom.: 1170 Cov.: 32 AF XY: 0.114 AC XY: 8349 AN XY: 73104

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0822

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0985 Hom.: 1074

Bravo AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.14

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: rs7856324; hg19: chr9-28366643;