2-148875987-CG-C

Position:

• chr2-148875987-CG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004522.3(KIF5C):​c.126+247del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 151,646 control chromosomes in the GnomAD database, including 35 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.021 (35 hom., cov: 32)
• Consequence: KIF5C NM_004522.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.920

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.

• BP6: Variant 2-148875987-CG-C is Benign according to our data. Variant chr2-148875987-CG-C is described in ClinVar as [Likely_benign]. Clinvar id is 1200063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0212 (3222/151646) while in subpopulation NFE AF= 0.0298 (2019/67742). AF 95% confidence interval is 0.0287. There are 35 homozygotes in gnomad4. There are 1545 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3222 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF5C	NM_004522.3	c.126+247del		intron_variant		ENST00000435030.6	NP_004513.1
KIF5C-AS1	XR_001739733.2	n.7330del		non_coding_transcript_exon_variant	4/4
KIF5C	XM_017004062.2	c.126+247del		intron_variant			XP_016859551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5C	ENST00000435030.6	c.126+247del		intron_variant		1	NM_004522.3	ENSP00000393379	P4
KIF5C-AS1	ENST00000601658.5	n.676+1238del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3226 AN: 151544 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00499

Gnomad AMI AF: 0.0826

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.0548

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0274

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0212 AC: 3222 AN: 151646 Hom.: 35 Cov.: 32 AF XY: 0.0208 AC XY: 1545 AN XY: 74110

Gnomad4 AFR AF: 0.00497

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0219

Gnomad4 FIN AF: 0.0285

Gnomad4 NFE AF: 0.0298

Gnomad4 OTH AF: 0.0271

Alfa AF: 0.0259 Hom.: 5

Bravo AF: 0.0210

Asia WGS AF: 0.00956 AC: 34 AN: 3464

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

Mar 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs560330687; hg19: chr2-149633556;