9-27948977-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001258282.3(LINGO2):c.1695G>A(p.Val565=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,613,866 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (8 hom.)
• Consequence: LINGO2 NM_001258282.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.394

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 9-27948977-C-T is Benign according to our data. Variant chr9-27948977-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.394 with no splicing effect.
• BS2: High AC in GnomAd at 164 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.1695G>A	p.Val565=	synonymous_variant	7/7	ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.1695G>A	p.Val565=	synonymous_variant	7/7		NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 164 AN: 151934 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00142 AC: 357 AN: 251008 Hom.: 3 AF XY: 0.00156 AC XY: 211 AN XY: 135624

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00209

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.00213

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00168 AC: 2454 AN: 1461814 Hom.: 8 Cov.: 32 AF XY: 0.00173 AC XY: 1257 AN XY: 727206

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000648

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00223

Gnomad4 FIN exome AF: 0.000562

Gnomad4 NFE exome AF: 0.00185

Gnomad4 OTH exome AF: 0.00190

GnomAD4 genome AF: 0.00109 AC: 165 AN: 152052 Hom.: 0 Cov.: 32 AF XY: 0.00109 AC XY: 81 AN XY: 74332

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000590

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.00185

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00181 Hom.: 0

Bravo AF: 0.00109

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00240

EpiControl AF: 0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

LINGO2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	8.2
Dann	Benign	0.78

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: rs113646467; hg19: chr9-27948975;