14-103562805-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000557172.5(KLC1):c.-2+821G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 657,944 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0099 (16 hom., cov: 33)
  • Exomes 𝑓: 0.013 (50 hom.)
• Consequence: KLC1 ENST00000557172.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.342

Genes affected

KLC1 (HGNC:6387): (kinesin light chain 1) Conventional kinesin is a tetrameric molecule composed of two heavy chains and two light chains, and transports various cargos along microtubules toward their plus ends. The heavy chains provide the motor activity, while the light chains bind to various cargos. This gene encodes a member of the kinesin light chain family. It associates with kinesin heavy chain through an N-terminal domain, and six tetratricopeptide repeat (TPR) motifs are thought to be involved in binding of cargos such as vesicles, mitochondria, and the Golgi complex. Thus, kinesin light chains function as adapter molecules and not motors per se. Although previously named "kinesin 2", this gene is not a member of the kinesin-2 / kinesin heavy chain subfamily of kinesin motor proteins. Extensive alternative splicing produces isoforms with different C-termini that are proposed to bind to different cargos; however, the full-length nature and/or biological validity of most of these variants have not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-103562805-G-A is Benign according to our data. Variant chr14-103562805-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1189057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1503 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLC1	ENST00000557172.5	c.-2+821G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00990 AC: 1503 AN: 151768 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00722

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.0130 AC: 6598 AN: 506068 Hom.: 50 Cov.: 7 AF XY: 0.0129 AC XY: 3210 AN XY: 249674

Gnomad4 AFR exome AF: 0.00288

Gnomad4 AMR exome AF: 0.00782

Gnomad4 ASJ exome AF: 0.0165

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00364

Gnomad4 FIN exome AF: 0.0193

Gnomad4 NFE exome AF: 0.0139

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.00988 AC: 1500 AN: 151876 Hom.: 16 Cov.: 33 AF XY: 0.00956 AC XY: 710 AN XY: 74234

Gnomad4 AFR AF: 0.00255

Gnomad4 AMR AF: 0.00721

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0136 Hom.: 0

Bravo AF: 0.00968

Asia WGS AF: 0.00116 AC: 4 AN: 3452

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.1
Dann	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs563228874; hg19: chr14-104029142;