11-66265241-T-TGGGGC

Position:

• chr11-66265241-T-TGGGGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000394067.7(KLC2):​c.1334+12_1334+16dup variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,011,708 control chromosomes in the GnomAD database, including 789 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (119 hom., cov: 33)
  • Exomes 𝑓: 0.034 (670 hom.)
• Consequence: KLC2 ENST00000394067.7 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-66265241-T-TGGGGC is Benign according to our data. Variant chr11-66265241-T-TGGGGC is described in ClinVar as [Benign]. Clinvar id is 1599161.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLC2	NM_001318734.2	c.1334+12_1334+16dup		splice_region_variant, intron_variant		ENST00000394067.7	NP_001305663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLC2	ENST00000394067.7	c.1334+12_1334+16dup		splice_region_variant, intron_variant		1	NM_001318734.2	ENSP00000377631	P1
KLC2-AS1	ENST00000530805.1	n.316-22_316-21insGCCCC		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5114 AN: 146444 Hom.: 119 Cov.: 33

Gnomad AFR AF: 0.00989

Gnomad AMI AF: 0.0445

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0555

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0270

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0497

Gnomad OTH AF: 0.0373

GnomAD3 exomes AF: 0.0352 AC: 8767 AN: 249282 Hom.: 202 AF XY: 0.0367 AC XY: 4967 AN XY: 135170

Gnomad AFR exome AF: 0.00812

Gnomad AMR exome AF: 0.0216

Gnomad ASJ exome AF: 0.0534

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0287

Gnomad FIN exome AF: 0.0405

Gnomad NFE exome AF: 0.0478

Gnomad OTH exome AF: 0.0376

GnomAD4 exome AF: 0.0343 AC: 29635 AN: 865136 Hom.: 670 Cov.: 30 AF XY: 0.0352 AC XY: 15774 AN XY: 448294

Gnomad4 AFR exome AF: 0.00896

Gnomad4 AMR exome AF: 0.0244

Gnomad4 ASJ exome AF: 0.0586

Gnomad4 EAS exome AF: 0.000145

Gnomad4 SAS exome AF: 0.0271

Gnomad4 FIN exome AF: 0.0527

Gnomad4 NFE exome AF: 0.0359

Gnomad4 OTH exome AF: 0.0377

GnomAD4 genome AF: 0.0349 AC: 5115 AN: 146572 Hom.: 119 Cov.: 33 AF XY: 0.0342 AC XY: 2449 AN XY: 71522

Gnomad4 AFR AF: 0.00986

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.0555

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0277

Gnomad4 FIN AF: 0.0418

Gnomad4 NFE AF: 0.0497

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0399 Hom.: 16

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

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: rs576416391; hg19: chr11-66032712;