2-148875314-C-A

Variant names:

• chr2-148875314-C-A
• rs7582522
• NM_004522.3:c.-304C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_004522.3(KIF5C):​c.-304C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 291,622 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (2 hom.)
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.44
• Publications: 0 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 2-148875314-C-A is Benign according to our data. Variant chr2-148875314-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1208967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00714 (1085/151954) while in subpopulation AFR AF = 0.0244 (1011/41498). AF 95% confidence interval is 0.0231. There are 7 homozygotes in GnomAd4. There are 494 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1085 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.-304C>A		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.-304C>A		5_prime_UTR	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-304C>A		5_prime_UTR	Exon 1 of 26	ENSP00000503013.1	O60282-1
	KIF5C	ENST00000677280.1		c.-304C>A		5_prime_UTR	Exon 1 of 26	ENSP00000503955.1	A0A7I2V492

Frequencies

GnomAD3 genomes AF: 0.00715 AC: 1085 AN: 151846 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000884

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00102 AC: 142 AN: 139668 Hom.: 2 Cov.: 0 AF XY: 0.000806 AC XY: 57 AN XY: 70710

African (AFR) AF: 0.0286 AC: 108 AN: 3776

American (AMR) AF: 0.00260 AC: 9 AN: 3456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5042

East Asian (EAS) AF: 0.00 AC: 0 AN: 11444

South Asian (SAS) AF: 0.00 AC: 0 AN: 3340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 724

European-Non Finnish (NFE) AF: 0.0000995 AC: 9 AN: 90464

Other (OTH) AF: 0.00174 AC: 16 AN: 9176

GnomAD4 genome AF: 0.00714 AC: 1085 AN: 151954 Hom.: 7 Cov.: 32 AF XY: 0.00665 AC XY: 494 AN XY: 74274

African (AFR) AF: 0.0244 AC: 1011 AN: 41498

American (AMR) AF: 0.00366 AC: 56 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000884 AC: 6 AN: 67882

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00576 Hom.: 0

Bravo AF: 0.00814

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.94
PhyloP100		1.4
PromoterAI		-0.18	Neutral

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

Other links and lift over

dbSNP: rs7582522; hg19: chr2-149632883;