2-148875576-CCCCCCACCCATCCCCGTG-C

Variant names:

• chr2-148875576-CCCCCCACCCATCCCCGTG-C
• rs534820275
• NM_004522.3:c.-36_-19delACCCATCCCCGTGCCCCC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004522.3(KIF5C):​c.-36_-19delACCCATCCCCGTGCCCCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0088 (4 hom., cov: 0)
  • Exomes 𝑓: 0.036 (304 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.20

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.

• BP6: Variant 2-148875576-CCCCCCACCCATCCCCGTG-C is Benign according to our data. Variant chr2-148875576-CCCCCCACCCATCCCCGTG-C is described in ClinVar as [Likely_benign]. Clinvar id is 421075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF5C	NM_004522.3	c.-36_-19delACCCATCCCCGTGCCCCC		5_prime_UTR_variant	Exon 1 of 26	ENST00000435030.6	NP_004513.1
KIF5C	XM_017004062.2	c.-36_-19delACCCATCCCCGTGCCCCC		5_prime_UTR_variant	Exon 1 of 26		XP_016859551.1
KIF5C-AS1	XR_001739733.2	n.7724_7741delCACGGGGATGGGTGGGGG		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5C	ENST00000435030	c.-36_-19delACCCATCCCCGTGCCCCC		5_prime_UTR_variant	Exon 1 of 26	1	NM_004522.3	ENSP00000393379.1

Frequencies

GnomAD3 genomes AF: 0.00879 AC: 1260 AN: 143416 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00209

Gnomad AMI AF: 0.00464

Gnomad AMR AF: 0.00938

Gnomad ASJ AF: 0.0103

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000948

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0135

GnomAD3 exomes AF: 0.0100 AC: 1178 AN: 117240 Hom.: 8 AF XY: 0.00972 AC XY: 628 AN XY: 64618

Gnomad AFR exome AF: 0.00262

Gnomad AMR exome AF: 0.00905

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00166

Gnomad FIN exome AF: 0.0100

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0125

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0356 AC: 14469 AN: 406010 Hom.: 304 AF XY: 0.0318 AC XY: 7096 AN XY: 223356

Gnomad4 AFR exome AF: 0.00669

Gnomad4 AMR exome AF: 0.00990

Gnomad4 ASJ exome AF: 0.0268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00202

Gnomad4 FIN exome AF: 0.0135

Gnomad4 NFE exome AF: 0.0553

Gnomad4 OTH exome AF: 0.0299

GnomAD4 genome AF: 0.00877 AC: 1259 AN: 143542 Hom.: 4 Cov.: 0 AF XY: 0.00817 AC XY: 570 AN XY: 69756

Gnomad4 AFR AF: 0.00209

Gnomad4 AMR AF: 0.00937

Gnomad4 ASJ AF: 0.0103

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000947

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0134

Alfa AF: 0.0113 Hom.: 2

Bravo AF: 0.00819

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 29, 2017

GeneDx

Significance: Likely benign

Review Status: flagged submission

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. -

not provided Benign:1

Sep 26, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs534820275; hg19: chr2-149633145;