11-66265241-TGGGGC-TGGGGCGGGGC

Variant names:

• chr11-66265242-GGGG-GGGGCG
• NM_001318734.2:c.1334+11_1334+12dupCG

Variant summary

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

The NM_001318734.2(KLC2):​c.1334+11_1334+12dupCG variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 NM_001318734.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• 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-AS1 (HGNC:40934): (KLC2 antisense RNA 1)

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: NM_001318734.2. 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
	KLC2	NM_001318734.2	MANE Select	c.1334+11_1334+12dupCG		intron	N/A	NP_001305663.1	Q9H0B6-1
	KLC2	NM_001134775.2		c.1334+11_1334+12dupCG		intron	N/A	NP_001128247.1	Q9H0B6-1
	KLC2	NM_001134776.2		c.1334+11_1334+12dupCG		intron	N/A	NP_001128248.1	Q9H0B6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLC2	ENST00000394067.7	TSL:1 MANE Select	c.1334+10_1334+11insCG		intron	N/A	ENSP00000377631.2	Q9H0B6-1
	KLC2	ENST00000316924.9	TSL:1	c.1334+10_1334+11insCG		intron	N/A	ENSP00000314837.5	Q9H0B6-1
	KLC2	ENST00000917341.1		c.1334+10_1334+11insCG		intron	N/A	ENSP00000587400.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 15

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.064

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: chr11-66032713;