chr2-148875574-G-C

Variant names:

• chr2-148875574-G-C
• rs557953832
• NM_004522.3:c.-44G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004522.3(KIF5C):​c.-44G>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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000057 (0 hom., cov: 33)
  • Exomes 𝑓: 0.011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).

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.-44G>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.-44G>C		5_prime_UTR	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-44G>C		5_prime_UTR	Exon 1 of 26	ENSP00000503013.1	O60282-1
	KIF5C	ENST00000677280.1		c.-44G>C		5_prime_UTR	Exon 1 of 26	ENSP00000503955.1	A0A7I2V492

Frequencies

GnomAD3 genomes AF: 0.0000569 AC: 8 AN: 140592 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000516

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000354

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00380 AC: 404 AN: 106178 AF XY: 0.00344

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.00948

Gnomad ASJ exome AF: 0.00417

Gnomad EAS exome AF: 0.00509

Gnomad FIN exome AF: 0.00376

Gnomad NFE exome AF: 0.00222

Gnomad OTH exome AF: 0.00564

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0109 AC: 3798 AN: 349204 Hom.: 0 Cov.: 3 AF XY: 0.0112 AC XY: 2157 AN XY: 191782

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

African (AFR) AF: 0.0117 AC: 104 AN: 8918

American (AMR) AF: 0.0236 AC: 479 AN: 20306

Ashkenazi Jewish (ASJ) AF: 0.00846 AC: 104 AN: 12294

East Asian (EAS) AF: 0.00206 AC: 33 AN: 16020

South Asian (SAS) AF: 0.0146 AC: 699 AN: 47846

European-Finnish (FIN) AF: 0.00701 AC: 209 AN: 29804

Middle Eastern (MID) AF: 0.0152 AC: 21 AN: 1380

European-Non Finnish (NFE) AF: 0.0101 AC: 1963 AN: 195070

Other (OTH) AF: 0.0106 AC: 186 AN: 17566

⚠️ 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: 0.0000569 AC: 8 AN: 140690 Hom.: 0 Cov.: 33 AF XY: 0.0000439 AC XY: 3 AN XY: 68314

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

African (AFR) AF: 0.0000514 AC: 2 AN: 38886

American (AMR) AF: 0.000210 AC: 3 AN: 14294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3276

East Asian (EAS) AF: 0.00 AC: 0 AN: 4332

South Asian (SAS) AF: 0.00 AC: 0 AN: 4172

European-Finnish (FIN) AF: 0.000354 AC: 3 AN: 8484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64140

Other (OTH) AF: 0.00 AC: 0 AN: 1970

⚠️ 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: 0.00485 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		0.18
PromoterAI		0.14	Neutral
Mutation Taster		=298/2	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: rs557953832; hg19: chr2-149633143;