rs576416391

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-66265241-TGGGGC-T
• chr11-66265241-TGGGGC-TGGGGCGGGGC
• chr11-66265241-TGGGGC-TGGGGCGGGGCGGGGC

Variant summary

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

The ENST00000394067.7(KLC2):​c.1334+7_1334+11delGGGGC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000577 in 866,848 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: KLC2 ENST00000394067.7 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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: 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: 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+16delGGGGC		intron	N/A	NP_001305663.1	Q9H0B6-1
	KLC2	NM_001134775.2		c.1334+12_1334+16delGGGGC		intron	N/A	NP_001128247.1	Q9H0B6-1
	KLC2	NM_001134776.2		c.1334+12_1334+16delGGGGC		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+7_1334+11delGGGGC		splice_region intron	N/A	ENSP00000377631.2	Q9H0B6-1
	KLC2	ENST00000316924.9	TSL:1	c.1334+7_1334+11delGGGGC		splice_region intron	N/A	ENSP00000314837.5	Q9H0B6-1
	KLC2	ENST00000917341.1		c.1334+7_1334+11delGGGGC		splice_region intron	N/A	ENSP00000587400.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000577 AC: 5 AN: 866848 Hom.: 0 AF XY: 0.00000668 AC XY: 3 AN XY: 449098

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21428

American (AMR) AF: 0.00 AC: 0 AN: 41256

Ashkenazi Jewish (ASJ) AF: 0.0000502 AC: 1 AN: 19918

East Asian (EAS) AF: 0.00 AC: 0 AN: 27634

South Asian (SAS) AF: 0.00 AC: 0 AN: 75116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4294

European-Non Finnish (NFE) AF: 0.00000502 AC: 3 AN: 598138

Other (OTH) AF: 0.0000265 AC: 1 AN: 37768

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.012

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;