chr9-28717575-T-C

Position:

• chr9-28717575-T-C

Variant summary

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

The NM_001258282.3(LINGO2):​c.-394-47295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,792 control chromosomes in the GnomAD database, including 9,880 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 0.35 (9880 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-394-47295A>G		intron_variant		ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-394-47295A>G		intron_variant			NM_001258282.3	ENSP00000513694	P1
LINGO2	ENST00000698401.1	c.-764-47295A>G		intron_variant				ENSP00000513696	P1
LINGO2	ENST00000698402.1	c.-549-47295A>G		intron_variant				ENSP00000513697	P1
LINGO2	ENST00000698404.1	c.-505-47295A>G		intron_variant				ENSP00000513699

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52868 AN: 151674 Hom.: 9864 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.349 AC: 52929 AN: 151792 Hom.: 9880 Cov.: 32 AF XY: 0.354 AC XY: 26252 AN XY: 74162

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.337

Alfa AF: 0.163 Hom.: 315

Bravo AF: 0.365

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.018
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7033345; hg19: chr9-28717573;