Variant 2-148875576-CCCCCCACCCATCCCCGTG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_004522.3(KIF5C):c.-36_-19del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0088 ( 4 hom., cov: 0)

Exomes 𝑓: 0.036 ( 304 hom. )

Failed GnomAD Quality Control

Consequence

KIF5C
NM_004522.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.20

Variant links:

Genes affected

KIF5C (HGNC:6325): (kinesin family member 5C) The protein encoded by this gene is a kinesin heavy chain subunit involved in the transport of cargo within the central nervous system. The encoded protein, which acts as a tetramer by associating with another heavy chain and two light chains, interacts with protein kinase CK2. Mutations in this gene have been associated with complex cortical dysplasia with other brain malformations-2. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Jul 2015]

KIF5C links:

KIF5C-AS1 (HGNC:40325): (KIF5C antisense RNA 1)

KIF5C-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 2-148875576-CCCCCCACCCATCCCCGTG-C is Benign according to our data. Variant chr2-148875576-CCCCCCACCCATCCCCGTG-C is described in ClinVar as [Likely_benign]. Clinvar id is 421075.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
KIF5C	NM_004522.3 linkuse as main transcript	c.-36_-19del	5_prime_UTR_variant	1/26	ENST00000435030.6	NP_004513.1
KIF5C-AS1	XR_001739733.2 linkuse as main transcript	n.7724_7741del	non_coding_transcript_exon_variant	4/4
KIF5C	XM_017004062.2 linkuse as main transcript	c.-36_-19del	5_prime_UTR_variant	1/26		XP_016859551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5C	ENST00000435030.6 linkuse as main transcript	c.-36_-19del		5_prime_UTR_variant	1/26	1	NM_004522.3	ENSP00000393379	P4	O60282-1
KIF5C-AS1	ENST00000601658.5 linkuse as main transcript	n.676+1632_676+1649del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00879

AC:

1260

AN:

143416

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00209

Gnomad AMI

AF:

0.00464

Gnomad AMR

AF:

0.00938

Gnomad ASJ

AF:

0.0103

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000948

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00658

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0135

GnomAD3 exomes

AF:

0.0100

AC:

1178

AN:

117240

Hom.:

AF XY:

0.00972

AC XY:

628

AN XY:

64618

show subpopulations

Gnomad AFR exome

AF:

0.00262

Gnomad AMR exome

AF:

0.00905

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00166

Gnomad FIN exome

AF:

0.0100

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0356

AC:

14469

AN:

406010

Hom.:

304

AF XY:

0.0318

AC XY:

7096

AN XY:

223356

show subpopulations

Gnomad4 AFR exome

AF:

0.00669

Gnomad4 AMR exome

AF:

0.00990

Gnomad4 ASJ exome

AF:

0.0268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00202

Gnomad4 FIN exome

AF:

0.0135

Gnomad4 NFE exome

AF:

0.0553

Gnomad4 OTH exome

AF:

0.0299

GnomAD4 genome

AF:

0.00877

AC:

1259

AN:

143542

Hom.:

Cov.:

AF XY:

0.00817

AC XY:

570

AN XY:

69756

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00937

Gnomad4 ASJ

AF:

0.0103

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000947

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.0134

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00819

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, flagged submission

clinical testing

GeneDx

Jun 29, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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