rs1554996989

Positions:

• chr11-66257085-AGCTAGGGCTGTGGATGAGCACTGCAGGAAGGCACTTCGGGGTCTATCAGAGGAAATTTTTGCTAACCTTCCGAGTTGTCTCAGAGCCAAACGTAGTAAGCTACCTGTCACCGGATGTGCTTGAGCTAAGGGCGCTGAACCACCTCTGTCAGAGACGGTGCATCCCCCACCGGATGTGACCCCGGGATGCGGAGCCTGGGGTCAGATCTGCGAGCCAG-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 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. 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

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]

LOC124902694 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-66257085-AGCTAGGGCTGTGGATGAGCACTGCAGGAAGGCACTTCGGGGTCTATCAGAGGAAATTTTTGCTAACCTTCCGAGTTGTCTCAGAGCCAAACGTAGTAAGCTACCTGTCACCGGATGTGCTTGAGCTAAGGGCGCTGAACCACCTCTGTCAGAGACGGTGCATCCCCCACCGGATGTGACCCCGGGATGCGGAGCCTGGGGTCAGATCTGCGAGCCAG-A is Pathogenic according to our data. Variant chr11-66257085-AGCTAGGGCTGTGGATGAGCACTGCAGGAAGGCACTTCGGGGTCTATCAGAGGAAATTTTTGCTAACCTTCCGAGTTGTCTCAGAGCCAAACGTAGTAAGCTACCTGTCACCGGATGTGCTTGAGCTAAGGGCGCTGAACCACCTCTGTCAGAGACGGTGCATCCCCCACCGGATGTGACCCCGGGATGCGGAGCCTGGGGTCAGATCTGCGAGCCAG-A is described in ClinVar as [Pathogenic]. Clinvar id is 222029.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-66257085-AGCTAGGGCTGTGGATGAGCACTGCAGGAAGGCACTTCGGGGTCTATCAGAGGAAATTTTTGCTAACCTTCCGAGTTGTCTCAGAGCCAAACGTAGTAAGCTACCTGTCACCGGATGTGCTTGAGCTAAGGGCGCTGAACCACCTCTGTCAGAGACGGTGCATCCCCCACCGGATGTGACCCCGGGATGCGGAGCCTGGGGTCAGATCTGCGAGCCAG-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLC2	NM_001134775.2	c.-451_-235del		5_prime_UTR_variant	1/16		NP_001128247.1
KLC2	XM_047427414.1	c.-48-1461_-48-1245del		intron_variant			XP_047283370.1
LOC124902694	XM_047427981.1	c.50+191_50+407del		intron_variant			XP_047283937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLC2	ENST00000417856	c.-451_-235del		5_prime_UTR_variant	1/16	5		ENSP00000399403.1
KLC2	ENST00000531240.5	c.-451_-235del		5_prime_UTR_variant	1/3	4		ENSP00000436577.1
KLC2	ENST00000417856.5	c.-451_-235del		non_coding_transcript_variant		5		ENSP00000399403.1

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spastic paraplegia, optic atropy, and neuropathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 31, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554996989; hg19: chr11-66024556;