2-148875789-C-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.126+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00736 in 1,568,610 control chromosomes in the GnomAD database, including 693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (100 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (593 hom.)
• Consequence: KIF5C NM_004522.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.476

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 2-148875789-C-T is Benign according to our data. Variant chr2-148875789-C-T is described in ClinVar as [Benign]. Clinvar id is 1235352.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF5C	NM_004522.3	c.126+46C>T		intron_variant		ENST00000435030.6
KIF5C-AS1	XR_001739733.2	n.7529G>A		non_coding_transcript_exon_variant	4/4
KIF5C	XM_017004062.2	c.126+46C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF5C	ENST00000435030.6	c.126+46C>T		intron_variant		1	NM_004522.3	P4
KIF5C-AS1	ENST00000601658.5	n.676+1437G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1527 AN: 152172 Hom.: 100 Cov.: 32

Gnomad AFR AF: 0.000892

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.0237 AC: 4354 AN: 183374 Hom.: 229 AF XY: 0.0202 AC XY: 2003 AN XY: 99300

Gnomad AFR exome AF: 0.000854

Gnomad AMR exome AF: 0.0707

Gnomad ASJ exome AF: 0.000815

Gnomad EAS exome AF: 0.159

Gnomad SAS exome AF: 0.00402

Gnomad FIN exome AF: 0.00374

Gnomad NFE exome AF: 0.000463

Gnomad OTH exome AF: 0.0147

GnomAD4 exome AF: 0.00707 AC: 10017 AN: 1416330 Hom.: 593 Cov.: 34 AF XY: 0.00670 AC XY: 4691 AN XY: 700018

Gnomad4 AFR exome AF: 0.000493

Gnomad4 AMR exome AF: 0.0634

Gnomad4 ASJ exome AF: 0.000558

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.00453

Gnomad4 FIN exome AF: 0.00441

Gnomad4 NFE exome AF: 0.000331

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.0100 AC: 1526 AN: 152280 Hom.: 100 Cov.: 32 AF XY: 0.0111 AC XY: 826 AN XY: 74454

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00141 Hom.: 2

Bravo AF: 0.0134

Asia WGS AF: 0.0530 AC: 182 AN: 3448

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

Jul 07, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	7.2
Dann	Uncertain	0.98

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: rs117284722; hg19: chr2-149633358;