NM_001258282.3:c.405C>T

Variant names:

• chr9-27950267-G-A
• rs111772526
• NM_001258282.3:c.405C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001258282.3(LINGO2):​c.405C>T​(p.Asp135Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,613,878 control chromosomes in the GnomAD database, including 3 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 0.0012 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: LINGO2 NM_001258282.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 3 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=2.69 with no splicing effect.
• BS2: High AC in GnomAd4 at 186 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.405C>T	p.Asp135Asp	synonymous	Exon 7 of 7	NP_001245211.1
	LINGO2	NM_001354574.2		c.405C>T	p.Asp135Asp	synonymous	Exon 6 of 6	NP_001341503.1
	LINGO2	NM_001354575.2		c.405C>T	p.Asp135Asp	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.405C>T	p.Asp135Asp	synonymous	Exon 7 of 7	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.405C>T	p.Asp135Asp	synonymous	Exon 6 of 6	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.405C>T	p.Asp135Asp	synonymous	Exon 7 of 7	ENSP00000513695.1

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 186 AN: 152178 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00207

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000969 AC: 243 AN: 250762 AF XY: 0.000967

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000955

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000786

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.00154 AC: 2249 AN: 1461582 Hom.: 1 Cov.: 32 AF XY: 0.00150 AC XY: 1094 AN XY: 727114

African (AFR) AF: 0.000358 AC: 12 AN: 33476

American (AMR) AF: 0.000917 AC: 41 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.000955 AC: 51 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00184 AC: 2051 AN: 1111756

Other (OTH) AF: 0.00154 AC: 93 AN: 60386

GnomAD4 genome AF: 0.00122 AC: 186 AN: 152296 Hom.: 2 Cov.: 32 AF XY: 0.00106 AC XY: 79 AN XY: 74468

African (AFR) AF: 0.000457 AC: 19 AN: 41560

American (AMR) AF: 0.000784 AC: 12 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00207 AC: 141 AN: 68028

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00120 Hom.: 1

Bravo AF: 0.00110

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.00160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.8
DANN	Benign	0.58
PhyloP100		2.7
Mutation Taster		=100/0	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: rs111772526; hg19: chr9-27950265;