2-148875592-G-C

Variant names:

• chr2-148875592-G-C
• rs1448746101
• NM_004522.3:c.-26G>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004522.3(KIF5C):​c.-26G>C variant causes a 5 prime UTR premature start codon gain 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 0)
  • Exomes 𝑓: 0.044 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.17

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 2-148875592-G-C is Benign according to our data. Variant chr2-148875592-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 507276.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF5C	NM_004522.3	c.-26G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 26	ENST00000435030.6	NP_004513.1
KIF5C	NM_004522.3	c.-26G>C		5_prime_UTR_variant	Exon 1 of 26	ENST00000435030.6	NP_004513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5C	ENST00000435030	c.-26G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 26	1	NM_004522.3	ENSP00000393379.1
KIF5C	ENST00000435030	c.-26G>C		5_prime_UTR_variant	Exon 1 of 26	1	NM_004522.3	ENSP00000393379.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 20 AN: 51694 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000456

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00122

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000403

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0114 AC: 632 AN: 55206 Hom.: 0 AF XY: 0.0106 AC XY: 344 AN XY: 32318

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.0511

Gnomad ASJ exome AF: 0.00566

Gnomad EAS exome AF: 0.0447

Gnomad SAS exome AF: 0.0139

Gnomad FIN exome AF: 0.00508

Gnomad NFE exome AF: 0.00754

Gnomad OTH exome AF: 0.0205

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0440 AC: 7191 AN: 163512 Hom.: 0 Cov.: 0 AF XY: 0.0421 AC XY: 3754 AN XY: 89146

Gnomad4 AFR exome AF: 0.0500

Gnomad4 AMR exome AF: 0.0834

Gnomad4 ASJ exome AF: 0.0230

Gnomad4 EAS exome AF: 0.0328

Gnomad4 SAS exome AF: 0.0618

Gnomad4 FIN exome AF: 0.0183

Gnomad4 NFE exome AF: 0.0441

Gnomad4 OTH exome AF: 0.0376

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000387 AC: 20 AN: 51726 Hom.: 0 Cov.: 0 AF XY: 0.000434 AC XY: 11 AN XY: 25362

Gnomad4 AFR AF: 0.000218

Gnomad4 AMR AF: 0.000455

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00122

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.000403

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000843 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 08, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.57
CADD	Benign	18
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: rs1448746101; hg19: chr2-149633161;