rs1554996989

Variant names:

• chr11-66257085-AGCTAGGGCTGTGGATGAGCACTGCAGGAAGGCACTTCGGGGTCTATCAGAGGAAATTTTTGCTAACCTTCCGAGTTGTCTCAGAGCCAAACGTAGTAAGCTACCTGTCACCGGATGTGCTTGAGCTAAGGGCGCTGAACCACCTCTGTCAGAGACGGTGCATCCCCCACCGGATGTGACCCCGGGATGCGGAGCCTGGGGTCAGATCTGCGAGCCAG-A
• rs1554996989
• NM_001134775.2:c.-451_-235del

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_001134775.2(KLC2):​c.-451_-235del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLC2 NM_001134775.2 5_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.11
• 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)

LOC124902694 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP5: Variant 11-66257085-AGCTAGGGCTGTGGATGAGCACTGCAGGAAGGCACTTCGGGGTCTATCAGAGGAAATTTTTGCTAACCTTCCGAGTTGTCTCAGAGCCAAACGTAGTAAGCTACCTGTCACCGGATGTGCTTGAGCTAAGGGCGCTGAACCACCTCTGTCAGAGACGGTGCATCCCCCACCGGATGTGACCCCGGGATGCGGAGCCTGGGGTCAGATCTGCGAGCCAG-A is Pathogenic according to our data. Variant chr11-66257085-AGCTAGGGCTGTGGATGAGCACTGCAGGAAGGCACTTCGGGGTCTATCAGAGGAAATTTTTGCTAACCTTCCGAGTTGTCTCAGAGCCAAACGTAGTAAGCTACCTGTCACCGGATGTGCTTGAGCTAAGGGCGCTGAACCACCTCTGTCAGAGACGGTGCATCCCCCACCGGATGTGACCCCGGGATGCGGAGCCTGGGGTCAGATCTGCGAGCCAG-A is described in ClinVar as Pathogenic. ClinVar VariationId is 222029.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134775.2. 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_001134775.2		c.-451_-235del		5_prime_UTR	Exon 1 of 16	NP_001128247.1	Q9H0B6-1
	KLC2	NM_001134775.2		c.-451_-235del		non_coding_transcript	N/A	NP_001128247.1	Q9H0B6-1
	KLC2	NM_001134775.2		c.-451_-235del		upstream_gene	N/A	NP_001128247.1	Q9H0B6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLC2	ENST00000417856.5	TSL:5	c.-451_-235del		5_prime_UTR	Exon 1 of 16	ENSP00000399403.1	Q9H0B6-1
	KLC2	ENST00000531240.5	TSL:4	c.-451_-235del		5_prime_UTR	Exon 1 of 3	ENSP00000436577.1	E9PI24
	KLC2	ENST00000417856.5	TSL:5	c.-451_-235del		non_coding_transcript	N/A	ENSP00000399403.1	Q9H0B6-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Spastic paraplegia, optic atropy, and neuropathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1554996989; hg19: chr11-66024556;