chr2-148875586-A-C

Variant names:

• chr2-148875586-A-C
• rs535977108
• NM_004522.3:c.-32A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004522.3(KIF5C):​c.-32A>C 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 0)
  • Exomes 𝑓: 0.099 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00100
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 2-148875586-A-C is Benign according to our data. Variant chr2-148875586-A-C is described in ClinVar as Benign. ClinVar VariationId is 1249855.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-32A>C		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.-32A>C		5_prime_UTR	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-32A>C		5_prime_UTR	Exon 1 of 26	ENSP00000503013.1	O60282-1
	KIF5C	ENST00000677280.1		c.-32A>C		5_prime_UTR	Exon 1 of 26	ENSP00000503955.1	A0A7I2V492

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 149 AN: 42452 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00217

Gnomad ASJ AF: 0.00560

Gnomad EAS AF: 0.00101

Gnomad SAS AF: 0.00240

Gnomad FIN AF: 0.00685

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00422

Gnomad OTH AF: 0.00356

GnomAD2 exomes AF: 0.0702 AC: 4358 AN: 62064 AF XY: 0.0664

Gnomad AFR exome AF: 0.0984

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.0536

Gnomad EAS exome AF: 0.208

Gnomad FIN exome AF: 0.0220

Gnomad NFE exome AF: 0.0480

Gnomad OTH exome AF: 0.0789

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0990 AC: 19870 AN: 200688 Hom.: 0 Cov.: 0 AF XY: 0.0958 AC XY: 10326 AN XY: 107826

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.121 AC: 550 AN: 4542

American (AMR) AF: 0.205 AC: 1935 AN: 9420

Ashkenazi Jewish (ASJ) AF: 0.0756 AC: 579 AN: 7656

East Asian (EAS) AF: 0.0699 AC: 573 AN: 8192

South Asian (SAS) AF: 0.126 AC: 3056 AN: 24304

European-Finnish (FIN) AF: 0.0450 AC: 801 AN: 17814

Middle Eastern (MID) AF: 0.0844 AC: 67 AN: 794

European-Non Finnish (NFE) AF: 0.0969 AC: 11446 AN: 118116

Other (OTH) AF: 0.0876 AC: 863 AN: 9850

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00351 AC: 149 AN: 42506 Hom.: 0 Cov.: 0 AF XY: 0.00333 AC XY: 70 AN XY: 21036

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00258 AC: 29 AN: 11256

American (AMR) AF: 0.00216 AC: 9 AN: 4160

Ashkenazi Jewish (ASJ) AF: 0.00560 AC: 6 AN: 1072

East Asian (EAS) AF: 0.00102 AC: 2 AN: 1968

South Asian (SAS) AF: 0.00240 AC: 3 AN: 1250

European-Finnish (FIN) AF: 0.00685 AC: 15 AN: 2190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 142

European-Non Finnish (NFE) AF: 0.00422 AC: 83 AN: 19684

Other (OTH) AF: 0.00351 AC: 2 AN: 570

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00119 Hom.: 0

ClinVar

ClinVar submissions

Significance: 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	-0.63
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		0.0010
PromoterAI		0.11	Neutral
Mutation Taster		=300/0	polymorphism

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: rs535977108; hg19: chr2-149633155;