rs6435387

Variant names:

• chr2-149008736-A-G
• rs6435387
• NM_004522.3:c.2550+669A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• complex cortical dysplasia with other brain malformations 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004522.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5C	NM_004522.3	MANE Select	c.2550+669A>G		intron	N/A	NP_004513.1	O60282-1
	KIF5C	NR_111932.2		n.1922+669A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5C	ENST00000435030.6	TSL:1 MANE Select	c.2550+669A>G		intron	N/A	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000464066.6	TSL:1	n.2415+669A>G		intron	N/A
	KIF5C	ENST00000482151.1	TSL:1	n.828+669A>G		intron	N/A

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

African (AFR) AF: 0.994 AC: 41304 AN: 41546

American (AMR) AF: 0.984 AC: 15050 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 3408 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5160 AN: 5160

South Asian (SAS) AF: 0.994 AC: 4792 AN: 4822

European-Finnish (FIN) AF: 0.963 AC: 10197 AN: 10594

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.967 AC: 65822 AN: 68034

Other (OTH) AF: 0.983 AC: 2079 AN: 2116

Alfa AF: 0.975 Hom.: 106424

Bravo AF: 0.980

Asia WGS AF: 0.995 AC: 3459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.61
DANN	Benign	0.44
PhyloP100		-1.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6435387;

hg19: chr2-149865250;