9-27950021-A-T

Variant names:

• chr9-27950021-A-T
• NM_001258282.3:c.651T>A
• LINGO2 p.Pro217Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001258282.3(LINGO2):​c.651T>A​(p.Pro217Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: LINGO2 NM_001258282.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-0.679 with no splicing effect.

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.651T>A	p.Pro217Pro	synonymous	Exon 7 of 7	NP_001245211.1	Q7L985
	LINGO2	NM_001354574.2		c.651T>A	p.Pro217Pro	synonymous	Exon 6 of 6	NP_001341503.1	Q7L985
	LINGO2	NM_001354575.2		c.651T>A	p.Pro217Pro	synonymous	Exon 7 of 7	NP_001341504.1	Q7L985

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.651T>A	p.Pro217Pro	synonymous	Exon 7 of 7	ENSP00000513694.1	Q7L985
	LINGO2	ENST00000379992.6	TSL:5	c.651T>A	p.Pro217Pro	synonymous	Exon 6 of 6	ENSP00000369328.1	Q7L985
	LINGO2	ENST00000698400.1		c.651T>A	p.Pro217Pro	synonymous	Exon 7 of 7	ENSP00000513695.1	Q7L985

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.90
DANN	Benign	0.44
PhyloP100		-0.68

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-27950019;