rs766321204

Variant names:

• chr11-66265252-T-G
• rs766321204
• NM_001318734.2:c.1334+17T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-66265252-T-G
• chr11-66265252-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001318734.2(KLC2):​c.1334+17T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000631 in 142,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (16 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLC2 NM_001318734.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.50
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-66265252-T-G is Benign according to our data. Variant chr11-66265252-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3627390.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1334+17T>G		intron	N/A	NP_001305663.1	Q9H0B6-1
	KLC2	NM_001134775.2		c.1334+17T>G		intron	N/A	NP_001128247.1	Q9H0B6-1
	KLC2	NM_001134776.2		c.1334+17T>G		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+17T>G		intron	N/A	ENSP00000377631.2	Q9H0B6-1
	KLC2	ENST00000316924.9	TSL:1	c.1334+17T>G		intron	N/A	ENSP00000314837.5	Q9H0B6-1
	KLC2	ENST00000917341.1		c.1334+17T>G		intron	N/A	ENSP00000587400.1

Frequencies

GnomAD3 genomes AF: 0.0000632 AC: 9 AN: 142370 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000782

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000183 AC: 45 AN: 246126 AF XY: 0.000217

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.000204

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000330

Gnomad NFE exome AF: 0.000270

Gnomad OTH exome AF: 0.000336

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00600 AC: 3646 AN: 608154 Hom.: 16 Cov.: 17 AF XY: 0.00548 AC XY: 1774 AN XY: 323966

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

African (AFR) AF: 0.00229 AC: 37 AN: 16188

American (AMR) AF: 0.000183 AC: 7 AN: 38190

Ashkenazi Jewish (ASJ) AF: 0.00229 AC: 36 AN: 15696

East Asian (EAS) AF: 0.000314 AC: 7 AN: 22322

South Asian (SAS) AF: 0.000716 AC: 49 AN: 68418

European-Finnish (FIN) AF: 0.000384 AC: 14 AN: 36476

Middle Eastern (MID) AF: 0.00389 AC: 13 AN: 3344

European-Non Finnish (NFE) AF: 0.00881 AC: 3351 AN: 380424

Other (OTH) AF: 0.00487 AC: 132 AN: 27096

⚠️ 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 AF: 0.0000631 AC: 9 AN: 142522 Hom.: 0 Cov.: 33 AF XY: 0.0000864 AC XY: 6 AN XY: 69458

African (AFR) AF: 0.0000747 AC: 3 AN: 40172

American (AMR) AF: 0.00 AC: 0 AN: 14500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3244

East Asian (EAS) AF: 0.00 AC: 0 AN: 4476

South Asian (SAS) AF: 0.00 AC: 0 AN: 4092

European-Finnish (FIN) AF: 0.000111 AC: 1 AN: 8996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.0000782 AC: 5 AN: 63942

Other (OTH) AF: 0.00 AC: 0 AN: 1990

Alfa AF: 0.00134 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.59
DANN	Benign	0.48
PhyloP100		-2.5
Mutation Taster		=16/84	disease causing

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: rs766321204; hg19: chr11-66032723; COSMIC: COSV57581873; COSMIC: COSV57581873;