rs6435220

Positions:

• chr2-149005165-G-A
• chr2-149005165-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004522.3(KIF5C):​c.2374-228G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,016 control chromosomes in the GnomAD database, including 36,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (36173 hom., cov: 31)
• Consequence: KIF5C NM_004522.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.992

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-149005165-G-A is Benign according to our data. Variant chr2-149005165-G-A is described in ClinVar as [Benign]. Clinvar id is 1252331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF5C	NM_004522.3	c.2374-228G>A		intron_variant		ENST00000435030.6	NP_004513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5C	ENST00000435030.6	c.2374-228G>A		intron_variant		1	NM_004522.3	ENSP00000393379.1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103753 AN: 151898 Hom.: 36119 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.683 AC: 103864 AN: 152016 Hom.: 36173 Cov.: 31 AF XY: 0.680 AC XY: 50497 AN XY: 74298

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.685

Alfa AF: 0.666 Hom.: 17775

Bravo AF: 0.686

Asia WGS AF: 0.541 AC: 1880 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.061
DANN	Benign	0.45

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: rs6435220; hg19: chr2-149861679;