Genetic Variant NM_001318734.2:c.1334+17T>G (chr11-66265252-T-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.50

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 Likely_benign. Variant got -6 ACMG points.

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 id is 3627390.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLC2	NM_001318734.2 link	c.1334+17T>G		intron_variant	Intron 11 of 15	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.1334+17T>G		intron_variant	Intron 11 of 15	1	NM_001318734.2	ENSP00000377631.2		Q9H0B6-1

Frequencies

GnomAD3 genomes

AF:

0.0000632

AC:

AN:

142370

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.000183

AC:

AN:

246126

Hom.:

AF XY:

0.000217

AC XY:

AN XY:

133586

show subpopulations

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 SAS exome

AF:

0.0000329

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.:

Cov.:

AF XY:

0.00548

AC XY:

1774

AN XY:

323966

show subpopulations

Gnomad4 AFR exome

AF:

0.00229

Gnomad4 AMR exome

AF:

0.000183

Gnomad4 ASJ exome

AF:

0.00229

Gnomad4 EAS exome

AF:

0.000314

Gnomad4 SAS exome

AF:

0.000716

Gnomad4 FIN exome

AF:

0.000384

Gnomad4 NFE exome

AF:

0.00881

Gnomad4 OTH exome

AF:

0.00487

GnomAD4 genome

AF:

0.0000631

AC:

AN:

142522

Hom.:

Cov.:

AF XY:

0.0000864

AC XY:

AN XY:

69458

show subpopulations

Gnomad4 AFR

AF:

0.0000747

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000111

Gnomad4 NFE

AF:

0.0000782

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00134

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.59

DANN

Benign

0.48

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