rs6435387

chr2-149008736-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004522.3(KIF5C):c.2550+669A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.978 in 152,240 control chromosomes in the GnomAD database, including 72,859 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.98 (72859 hom., cov: 30)
• Consequence: KIF5C NM_004522.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF5C	NM_004522.3	c.2550+669A>G		intron_variant		ENST00000435030.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF5C	ENST00000435030.6	c.2550+669A>G		intron_variant		1	NM_004522.3	P4

Frequencies

GnomAD3 genomes AF: 0.978 AC: 148798 AN: 152122 Hom.: 72800 Cov.: 30

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.982

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.978 AC: 148916 AN: 152240 Hom.: 72859 Cov.: 30 AF XY: 0.978 AC XY: 72794 AN XY: 74434

Gnomad4 AFR AF: 0.994

Gnomad4 AMR AF: 0.984

Gnomad4 ASJ AF: 0.982

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.994

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.967

Gnomad4 OTH AF: 0.983

Alfa AF: 0.972 Hom.: 46466

Bravo AF: 0.980

Asia WGS AF: 0.995 AC: 3459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.61
Dann	Benign	0.44

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: rs6435387; hg19: chr2-149865250;