11-66265200-A-G

Variant names:

• chr11-66265200-A-G
• rs1226798548
• NM_001318734.2:c.1299A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001318734.2(KLC2):​c.1299A>G​(p.Glu433Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000553 in 1,447,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: KLC2 NM_001318734.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=1.61 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318734.2. 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_001318734.2	MANE Select	c.1299A>G	p.Glu433Glu	synonymous	Exon 11 of 16	NP_001305663.1	Q9H0B6-1
	KLC2	NM_001134775.2		c.1299A>G	p.Glu433Glu	synonymous	Exon 11 of 16	NP_001128247.1	Q9H0B6-1
	KLC2	NM_001134776.2		c.1299A>G	p.Glu433Glu	synonymous	Exon 11 of 16	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.1299A>G	p.Glu433Glu	synonymous	Exon 11 of 16	ENSP00000377631.2	Q9H0B6-1
	KLC2	ENST00000316924.9	TSL:1	c.1299A>G	p.Glu433Glu	synonymous	Exon 11 of 16	ENSP00000314837.5	Q9H0B6-1
	KLC2	ENST00000917341.1		c.1299A>G	p.Glu433Glu	synonymous	Exon 11 of 16	ENSP00000587400.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000553 AC: 8 AN: 1447298 Hom.: 0 Cov.: 34 AF XY: 0.00000695 AC XY: 5 AN XY: 719612

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.00 AC: 0 AN: 44380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25516

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.00000727 AC: 8 AN: 1100968

Other (OTH) AF: 0.00 AC: 0 AN: 59496

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1226798548; hg19: chr11-66032671;