2-148875587-T-C

Variant names:

• chr2-148875587-T-C
• rs1558866657
• NM_004522.3:c.-31T>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.-31T>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 0.000039 (0 hom., cov: 30)
  • Exomes 𝑓: 0.030 (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: 0.269
• 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=-0.68).
• BP6: Variant 2-148875587-T-C is Benign according to our data. Variant chr2-148875587-T-C is described in ClinVar as Benign. ClinVar VariationId is 1277980.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.-31T>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.-31T>C		5_prime_UTR	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-31T>C		5_prime_UTR	Exon 1 of 26	ENSP00000503013.1	O60282-1
	KIF5C	ENST00000677280.1		c.-31T>C		5_prime_UTR	Exon 1 of 26	ENSP00000503955.1	A0A7I2V492

Frequencies

GnomAD3 genomes AF: 0.0000393 AC: 4 AN: 101672 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000381

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000446

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000207

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00115 AC: 96 AN: 83652 AF XY: 0.00107

Gnomad AFR exome AF: 0.000279

Gnomad AMR exome AF: 0.00313

Gnomad ASJ exome AF: 0.000824

Gnomad EAS exome AF: 0.00217

Gnomad FIN exome AF: 0.00175

Gnomad NFE exome AF: 0.000549

Gnomad OTH exome AF: 0.00202

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0297 AC: 7446 AN: 250332 Hom.: 0 Cov.: 0 AF XY: 0.0266 AC XY: 3603 AN XY: 135276

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

African (AFR) AF: 0.0283 AC: 186 AN: 6568

American (AMR) AF: 0.0212 AC: 260 AN: 12272

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 137 AN: 8674

East Asian (EAS) AF: 0.0151 AC: 150 AN: 9942

South Asian (SAS) AF: 0.00979 AC: 330 AN: 33722

European-Finnish (FIN) AF: 0.00546 AC: 127 AN: 23266

Middle Eastern (MID) AF: 0.0239 AC: 23 AN: 962

European-Non Finnish (NFE) AF: 0.0414 AC: 5919 AN: 143064

Other (OTH) AF: 0.0265 AC: 314 AN: 11862

⚠️ 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: 0.0000393 AC: 4 AN: 101716 Hom.: 0 Cov.: 30 AF XY: 0.0000205 AC XY: 1 AN XY: 48794

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

African (AFR) AF: 0.00 AC: 0 AN: 27332

American (AMR) AF: 0.00 AC: 0 AN: 9858

Ashkenazi Jewish (ASJ) AF: 0.000381 AC: 1 AN: 2626

East Asian (EAS) AF: 0.00 AC: 0 AN: 3744

South Asian (SAS) AF: 0.00 AC: 0 AN: 3144

European-Finnish (FIN) AF: 0.000446 AC: 2 AN: 4484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.0000207 AC: 1 AN: 48238

Other (OTH) AF: 0.00 AC: 0 AN: 1442

⚠️ 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.

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	-0.68
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		0.27
PromoterAI		0.018	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: rs1558866657; hg19: chr2-149633156;