chr9-28717575-T-C

Variant names:

• chr9-28717575-T-C
• rs7033345
• NM_001258282.3:c.-394-47295A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.-394-47295A>G		intron	N/A	NP_001245211.1	Q7L985
	LINGO2	NM_001354574.2		c.-361-47295A>G		intron	N/A	NP_001341503.1	Q7L985
	LINGO2	NM_001354575.2		c.-394-47295A>G		intron	N/A	NP_001341504.1	Q7L985

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-394-47295A>G		intron	N/A	ENSP00000513694.1	Q7L985
	LINGO2	ENST00000698401.1		c.-764-47295A>G		intron	N/A	ENSP00000513696.1	Q7L985
	LINGO2	ENST00000698402.1		c.-549-47295A>G		intron	N/A	ENSP00000513697.1	Q7L985

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

African (AFR) AF: 0.456 AC: 18894 AN: 41408

American (AMR) AF: 0.460 AC: 6994 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3464

East Asian (EAS) AF: 0.407 AC: 2096 AN: 5148

South Asian (SAS) AF: 0.305 AC: 1468 AN: 4808

European-Finnish (FIN) AF: 0.338 AC: 3568 AN: 10568

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18348 AN: 67864

Other (OTH) AF: 0.337 AC: 709 AN: 2106

Alfa AF: 0.179 Hom.: 386

Bravo AF: 0.365

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.018
DANN	Benign	0.37
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs7033345; hg19: chr9-28717573;