rs10968215

Variant names:

• chr9-27940162-C-T
• rs10968215
• NM_001258282.3:c.*8689G>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.*8689G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,620 control chromosomes in the GnomAD database, including 6,528 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 0.28 (6528 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LINGO2 NM_001258282.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• 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]

ENSG00000260412 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.*8689G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.*8689G>A		3_prime_UTR_variant	Exon 7 of 7		NM_001258282.3	ENSP00000513694.1
ENSG00000260412	ENST00000566293.1	n.4336G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
LINGO2	ENST00000698405.1	n.813-694G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42809 AN: 151504 Hom.: 6526 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.330

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.282 AC: 42825 AN: 151620 Hom.: 6528 Cov.: 32 AF XY: 0.283 AC XY: 20931 AN XY: 74058

African (AFR) AF: 0.177 AC: 7333 AN: 41324

American (AMR) AF: 0.296 AC: 4510 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3464

East Asian (EAS) AF: 0.332 AC: 1712 AN: 5156

South Asian (SAS) AF: 0.421 AC: 2027 AN: 4812

European-Finnish (FIN) AF: 0.223 AC: 2322 AN: 10434

Middle Eastern (MID) AF: 0.459 AC: 133 AN: 290

European-Non Finnish (NFE) AF: 0.333 AC: 22645 AN: 67904

Other (OTH) AF: 0.327 AC: 684 AN: 2094

Alfa AF: 0.302 Hom.: 1030

Bravo AF: 0.277

Asia WGS AF: 0.368 AC: 1281 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.39
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs10968215; hg19: chr9-27940160;