11-66265241-TGGGGC-TGGGGCGGGGC

Variant names:

• chr11-66265241-T-TGGGGC
• rs576416391
• NM_001318734.2:c.1334+12_1334+16dupGGGGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000394067.7(KLC2):​c.1334+6_1334+7insGGGGC 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
• 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: Benign. The variant received -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 VariationId 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.

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
	KLC2	NM_001318734.2	MANE Select	c.1334+12_1334+16dupGGGGC		intron	N/A	NP_001305663.1	Q9H0B6-1
	KLC2	NM_001134775.2		c.1334+12_1334+16dupGGGGC		intron	N/A	NP_001128247.1	Q9H0B6-1
	KLC2	NM_001134776.2		c.1334+12_1334+16dupGGGGC		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+6_1334+7insGGGGC		splice_region intron	N/A	ENSP00000377631.2	Q9H0B6-1
	KLC2	ENST00000316924.9	TSL:1	c.1334+6_1334+7insGGGGC		splice_region intron	N/A	ENSP00000314837.5	Q9H0B6-1
	KLC2	ENST00000917341.1		c.1334+6_1334+7insGGGGC		splice_region intron	N/A	ENSP00000587400.1

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

GnomAD2 exomes AF: 0.0352 AC: 8767 AN: 249282 AF XY: 0.0367

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 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

African (AFR) AF: 0.00896 AC: 192 AN: 21422

American (AMR) AF: 0.0244 AC: 1005 AN: 41240

Ashkenazi Jewish (ASJ) AF: 0.0586 AC: 1165 AN: 19884

East Asian (EAS) AF: 0.000145 AC: 4 AN: 27634

South Asian (SAS) AF: 0.0271 AC: 2035 AN: 75078

European-Finnish (FIN) AF: 0.0527 AC: 2175 AN: 41266

Middle Eastern (MID) AF: 0.0575 AC: 246 AN: 4280

European-Non Finnish (NFE) AF: 0.0359 AC: 21392 AN: 596640

Other (OTH) AF: 0.0377 AC: 1421 AN: 37692

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

African (AFR) AF: 0.00986 AC: 395 AN: 40062

American (AMR) AF: 0.0382 AC: 568 AN: 14878

Ashkenazi Jewish (ASJ) AF: 0.0555 AC: 189 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 4754

South Asian (SAS) AF: 0.0277 AC: 123 AN: 4438

European-Finnish (FIN) AF: 0.0418 AC: 392 AN: 9386

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0497 AC: 3302 AN: 66418

Other (OTH) AF: 0.0369 AC: 76 AN: 2060

Alfa AF: 0.0399 Hom.: 16

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs576416391; hg19: chr11-66032712;