chr11-66258651-G-G

Variant names:

• chr11-66258651-G-G
• ENST00000394067.7:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000394067.7(KLC2):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLC2 ENST00000394067.7 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 0 publications found

Genes affected

KLC2 (HGNC:20716): (kinesin light chain 2) The protein encoded by this gene is a light chain of kinesin, a molecular motor responsible for moving vesicles and organelles along microtubules. Defects in this gene are a cause of spastic paraplegia, optic atrophy, and neuropathy (SPOAN) syndrome. [provided by RefSeq, Mar 2016]

KLC2 Gene-Disease associations (from GenCC):

• spastic paraplegia, optic atropy, and neuropathy

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000255320 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394067.7. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLC2	ENST00000394067.7	TSL:1 MANE Select	c.		exon_region	Exon 2 of 16	ENSP00000377631.2	Q9H0B6-1
	KLC2	ENST00000316924.9	TSL:1	c.		exon_region	Exon 2 of 16	ENSP00000314837.5	Q9H0B6-1
	KLC2	ENST00000917341.1		c.		exon_region	Exon 2 of 16	ENSP00000587400.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

Splicing

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: chr11-66026122;