rs6738277

chr2-148997446-A-G

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.2100+106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 1,558,242 control chromosomes in the GnomAD database, including 333,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35594 hom., cov: 32)
  • Exomes 𝑓: 0.65 (297469 hom.)
• Consequence: KIF5C NM_004522.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0820

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-148997446-A-G is Benign according to our data. Variant chr2-148997446-A-G is described in ClinVar as [Benign]. Clinvar id is 1240665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF5C	NM_004522.3	c.2100+106A>G		intron_variant		ENST00000435030.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF5C	ENST00000435030.6	c.2100+106A>G		intron_variant		1	NM_004522.3	P4

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103051 AN: 151908 Hom.: 35545 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.686

GnomAD3 exomes AF: 0.638 AC: 118459 AN: 185594 Hom.: 38799 AF XY: 0.643 AC XY: 63528 AN XY: 98776

Gnomad AFR exome AF: 0.790

Gnomad AMR exome AF: 0.604

Gnomad ASJ exome AF: 0.707

Gnomad EAS exome AF: 0.292

Gnomad SAS exome AF: 0.687

Gnomad FIN exome AF: 0.662

Gnomad NFE exome AF: 0.657

Gnomad OTH exome AF: 0.664

GnomAD4 exome AF: 0.647 AC: 909943 AN: 1406216 Hom.: 297469 Cov.: 28 AF XY: 0.649 AC XY: 449973 AN XY: 692924

Gnomad4 AFR exome AF: 0.788

Gnomad4 AMR exome AF: 0.611

Gnomad4 ASJ exome AF: 0.719

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.690

Gnomad4 FIN exome AF: 0.663

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.647

GnomAD4 genome AF: 0.679 AC: 103158 AN: 152026 Hom.: 35594 Cov.: 32 AF XY: 0.675 AC XY: 50159 AN XY: 74292

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.682

Alfa AF: 0.667 Hom.: 38895

Bravo AF: 0.680

Asia WGS AF: 0.544 AC: 1890 AN: 3476

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	-0.90
Cadd	Benign	1.4
Dann	Benign	0.39

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: rs6738277; hg19: chr2-149853960; COSMIC: COSV68483105; COSMIC: COSV68483105;