2-148875586-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004522.3(KIF5C):c.-32A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 0)
  • Exomes 𝑓: 0.099 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00100

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 2-148875586-A-C is Benign according to our data. Variant chr2-148875586-A-C is described in ClinVar as [Benign]. Clinvar id is 1249855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 4358 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF5C	NM_004522.3	c.-32A>C		5_prime_UTR_variant	1/26	ENST00000435030.6
KIF5C-AS1	XR_001739733.2	n.7732T>G		non_coding_transcript_exon_variant	4/4
KIF5C	XM_017004062.2	c.-32A>C		5_prime_UTR_variant	1/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF5C	ENST00000435030.6	c.-32A>C		5_prime_UTR_variant	1/26	1	NM_004522.3	P4
KIF5C-AS1	ENST00000601658.5	n.676+1640T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 149 AN: 42452 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00217

Gnomad ASJ AF: 0.00560

Gnomad EAS AF: 0.00101

Gnomad SAS AF: 0.00240

Gnomad FIN AF: 0.00685

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00422

Gnomad OTH AF: 0.00356

GnomAD3 exomes AF: 0.0702 AC: 4358 AN: 62064 Hom.: 0 AF XY: 0.0664 AC XY: 2402 AN XY: 36188

Gnomad AFR exome AF: 0.0984

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.0536

Gnomad EAS exome AF: 0.208

Gnomad SAS exome AF: 0.0890

Gnomad FIN exome AF: 0.0220

Gnomad NFE exome AF: 0.0480

Gnomad OTH exome AF: 0.0789

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0990 AC: 19870 AN: 200688 Hom.: 0 Cov.: 0 AF XY: 0.0958 AC XY: 10326 AN XY: 107826

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.0756

Gnomad4 EAS exome AF: 0.0699

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0450

Gnomad4 NFE exome AF: 0.0969

Gnomad4 OTH exome AF: 0.0876

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00351 AC: 149 AN: 42506 Hom.: 0 Cov.: 0 AF XY: 0.00333 AC XY: 70 AN XY: 21036

Gnomad4 AFR AF: 0.00258

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00560

Gnomad4 EAS AF: 0.00102

Gnomad4 SAS AF: 0.00240

Gnomad4 FIN AF: 0.00685

Gnomad4 NFE AF: 0.00422

Gnomad4 OTH AF: 0.00351

Alfa AF: 0.00119 Hom.: 0

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

Aug 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	15
Dann	Benign	0.80

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: rs535977108; hg19: chr2-149633155;