NM_004522.3:c.-36_-19delACCCATCCCCGTGCCCCC

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 421075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1259 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004522.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5C	NM_004522.3	MANE Select	c.-36_-19delACCCATCCCCGTGCCCCC		5_prime_UTR	Exon 1 of 26	NP_004513.1	O60282-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5C	ENST00000435030.6	TSL:1 MANE Select	c.-36_-19delACCCATCCCCGTGCCCCC		5_prime_UTR	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-36_-19delACCCATCCCCGTGCCCCC		5_prime_UTR	Exon 1 of 26	ENSP00000503013.1	O60282-1
	KIF5C	ENST00000677280.1		c.-36_-19delACCCATCCCCGTGCCCCC		5_prime_UTR	Exon 1 of 26	ENSP00000503955.1	A0A7I2V492

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

GnomAD2 exomes AF: 0.0100 AC: 1178 AN: 117240 AF XY: 0.00972

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 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

African (AFR) AF: 0.00669 AC: 68 AN: 10166

American (AMR) AF: 0.00990 AC: 259 AN: 26174

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 367 AN: 13714

East Asian (EAS) AF: 0.00 AC: 0 AN: 16868

South Asian (SAS) AF: 0.00202 AC: 116 AN: 57508

European-Finnish (FIN) AF: 0.0135 AC: 451 AN: 33294

Middle Eastern (MID) AF: 0.0392 AC: 63 AN: 1608

European-Non Finnish (NFE) AF: 0.0553 AC: 12551 AN: 226822

Other (OTH) AF: 0.0299 AC: 594 AN: 19856

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

African (AFR) AF: 0.00209 AC: 84 AN: 40270

American (AMR) AF: 0.00937 AC: 138 AN: 14730

Ashkenazi Jewish (ASJ) AF: 0.0103 AC: 34 AN: 3306

East Asian (EAS) AF: 0.00 AC: 0 AN: 4322

South Asian (SAS) AF: 0.000947 AC: 4 AN: 4224

European-Finnish (FIN) AF: 0.0105 AC: 94 AN: 8964

Middle Eastern (MID) AF: 0.00709 AC: 2 AN: 282

European-Non Finnish (NFE) AF: 0.0135 AC: 872 AN: 64564

Other (OTH) AF: 0.0134 AC: 27 AN: 2018

Alfa AF: 0.0113 Hom.: 2

Bravo AF: 0.00819

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

Splicing

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

Other links and lift over

dbSNP: rs534820275; hg19: chr2-149633145;