Genetic Variant KLC2:p.Ser436Ser (chr11-66265209-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_001318734.2(KLC2):c.1308C>T(p.Ser436Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.00375 in 1,514,820 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 19 hom. )

Consequence

KLC2
NM_001318734.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.12

Variant links:

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 links:

KLC2-AS1 (HGNC:40934): (KLC2 antisense RNA 1)

KLC2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 11-66265209-C-T is Benign according to our data. Variant chr11-66265209-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 774626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLC2	NM_001318734.2 link	c.1308C>T	p.Ser436Ser	synonymous_variant	Exon 11 of 16	ENST00000394067.7	NP_001305663.1	Q9H0B6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLC2	ENST00000394067.7 link	c.1308C>T	p.Ser436Ser	synonymous_variant	Exon 11 of 16	1	NM_001318734.2	ENSP00000377631.2		Q9H0B6-1

Frequencies

GnomAD3 genomes

AF:

0.00257

AC:

386

AN:

149932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000632

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000928

Gnomad ASJ

AF:

0.00204

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00171

Gnomad FIN

AF:

0.00560

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00404

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.00283

AC:

710

AN:

250974

Hom.:

AF XY:

0.00301

AC XY:

409

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.000872

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00310

Gnomad FIN exome

AF:

0.00545

Gnomad NFE exome

AF:

0.00379

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00388

AC:

5289

AN:

1364754

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

2609

AN XY:

678970

show subpopulations

Gnomad4 AFR exome

AF:

0.000512

Gnomad4 AMR exome

AF:

0.000590

Gnomad4 ASJ exome

AF:

0.00204

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00301

Gnomad4 FIN exome

AF:

0.00588

Gnomad4 NFE exome

AF:

0.00428

Gnomad4 OTH exome

AF:

0.00312

GnomAD4 genome

AF:

0.00257

AC:

386

AN:

150066

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

195

AN XY:

73318

show subpopulations

Gnomad4 AFR

AF:

0.000630

Gnomad4 AMR

AF:

0.000927

Gnomad4 ASJ

AF:

0.00204

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00171

Gnomad4 FIN

AF:

0.00560

Gnomad4 NFE

AF:

0.00404

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00288

Hom.:

Bravo

AF:

0.00199

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00354

EpiControl

AF:

0.00403

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KLC2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over