2-148875582-A-C

Position:

• chr2-148875582-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_004522.3(KIF5C):​c.-36A>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 0.0070 (0 hom., cov: 0)
  • Exomes 𝑓: 0.16 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0630

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 2-148875582-A-C is Benign according to our data. Variant chr2-148875582-A-C is described in ClinVar as [Benign]. Clinvar id is 683963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF5C	NM_004522.3	c.-36A>C		5_prime_UTR_variant	1/26	ENST00000435030.6	NP_004513.1
KIF5C-AS1	XR_001739733.2	n.7736T>G		non_coding_transcript_exon_variant	4/4
KIF5C	XM_017004062.2	c.-36A>C		5_prime_UTR_variant	1/26		XP_016859551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5C	ENST00000435030.6	c.-36A>C		5_prime_UTR_variant	1/26	1	NM_004522.3	ENSP00000393379	P4
KIF5C-AS1	ENST00000601658.5	n.676+1644T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 357 AN: 51320 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00599

Gnomad AMI AF: 0.00385

Gnomad AMR AF: 0.00564

Gnomad ASJ AF: 0.00820

Gnomad EAS AF: 0.00272

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.00888

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00818

Gnomad OTH AF: 0.00448

GnomAD3 exomes AF: 0.155 AC: 9541 AN: 61730 Hom.: 1 AF XY: 0.144 AC XY: 5038 AN XY: 34974

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.317

Gnomad SAS exome AF: 0.150

Gnomad FIN exome AF: 0.0494

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.187

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.161 AC: 31237 AN: 193664 Hom.: 3 Cov.: 4 AF XY: 0.156 AC XY: 16076 AN XY: 103322

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.0784

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00697 AC: 358 AN: 51342 Hom.: 0 Cov.: 0 AF XY: 0.00668 AC XY: 167 AN XY: 25012

Gnomad4 AFR AF: 0.00605

Gnomad4 AMR AF: 0.00564

Gnomad4 ASJ AF: 0.00820

Gnomad4 EAS AF: 0.00272

Gnomad4 SAS AF: 0.00458

Gnomad4 FIN AF: 0.00888

Gnomad4 NFE AF: 0.00818

Gnomad4 OTH AF: 0.00444

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.87

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: rs762542110; hg19: chr2-149633151;