chr9-27948977-C-T

Variant names:

• chr9-27948977-C-T
• rs113646467
• NM_001258282.3:c.1695G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001258282.3(LINGO2):​c.1695G>A​(p.Val565Val) 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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 GnomAd4 at 165 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.1695G>A	p.Val565Val	synonymous	Exon 7 of 7	NP_001245211.1
	LINGO2	NM_001354574.2		c.1695G>A	p.Val565Val	synonymous	Exon 6 of 6	NP_001341503.1
	LINGO2	NM_001354575.2		c.1695G>A	p.Val565Val	synonymous	Exon 7 of 7	NP_001341504.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.1695G>A	p.Val565Val	synonymous	Exon 7 of 7	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.1695G>A	p.Val565Val	synonymous	Exon 6 of 6	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.1695G>A	p.Val565Val	synonymous	Exon 7 of 7	ENSP00000513695.1

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

GnomAD2 exomes AF: 0.00142 AC: 357 AN: 251008 AF XY: 0.00156

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 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

African (AFR) AF: 0.000179 AC: 6 AN: 33478

American (AMR) AF: 0.000648 AC: 29 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00223 AC: 192 AN: 86256

European-Finnish (FIN) AF: 0.000562 AC: 30 AN: 53416

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.00185 AC: 2058 AN: 1111980

Other (OTH) AF: 0.00190 AC: 115 AN: 60392

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

African (AFR) AF: 0.000337 AC: 14 AN: 41490

American (AMR) AF: 0.000590 AC: 9 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4810

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10556

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00185 AC: 126 AN: 67982

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

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

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LINGO2: BP4, BP7, BS2

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.2
DANN	Benign	0.78
PhyloP100		0.39
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs113646467; hg19: chr9-27948975;