2-148875587-T-A

Position:

• chr2-148875587-T-A

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.-31T>A 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000098 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.269

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=-0.59).
• BP6: Variant 2-148875587-T-A is Benign according to our data. Variant chr2-148875587-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1203882.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF5C	NM_004522.3	c.-31T>A		5_prime_UTR_variant	1/26	ENST00000435030.6	NP_004513.1
KIF5C-AS1	XR_001739733.2	n.7731A>T		non_coding_transcript_exon_variant	4/4
KIF5C	XM_017004062.2	c.-31T>A		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.-31T>A		5_prime_UTR_variant	1/26	1	NM_004522.3	ENSP00000393379	P4
KIF5C-AS1	ENST00000601658.5	n.676+1639A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 101976 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000317

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000359 AC: 30 AN: 83652 Hom.: 0 AF XY: 0.000273 AC XY: 13 AN XY: 47578

Gnomad AFR exome AF: 0.000557

Gnomad AMR exome AF: 0.000712

Gnomad ASJ exome AF: 0.000824

Gnomad EAS exome AF: 0.000542

Gnomad SAS exome AF: 0.000406

Gnomad FIN exome AF: 0.000153

Gnomad NFE exome AF: 0.000231

Gnomad OTH exome AF: 0.000506

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00353 AC: 926 AN: 262460 Hom.: 0 Cov.: 0 AF XY: 0.00310 AC XY: 439 AN XY: 141586

Gnomad4 AFR exome AF: 0.00485

Gnomad4 AMR exome AF: 0.00635

Gnomad4 ASJ exome AF: 0.00378

Gnomad4 EAS exome AF: 0.00291

Gnomad4 SAS exome AF: 0.00128

Gnomad4 FIN exome AF: 0.000713

Gnomad4 NFE exome AF: 0.00416

Gnomad4 OTH exome AF: 0.00417

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000980 AC: 1 AN: 102030 Hom.: 0 Cov.: 30 AF XY: 0.0000204 AC XY: 1 AN XY: 48962

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000317

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.92

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: rs1558866657; hg19: chr2-149633156;