2-148875574-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004522.3(KIF5C):​c.-44G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 354,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: KIF5C NM_004522.3 5_prime_UTR_premature_start_codon_gain
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

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>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	NP_004513.1	O60282-1
	KIF5C	NM_004522.3	MANE Select	c.-44G>T		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>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000435030.6	TSL:1 MANE Select	c.-44G>T		5_prime_UTR	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-44G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	ENSP00000503013.1	O60282-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000282 AC: 1 AN: 354416 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 194874

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

African (AFR) AF: 0.00 AC: 0 AN: 8966

American (AMR) AF: 0.00 AC: 0 AN: 20492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12384

East Asian (EAS) AF: 0.00 AC: 0 AN: 16062

South Asian (SAS) AF: 0.00 AC: 0 AN: 49128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1398

European-Non Finnish (NFE) AF: 0.00000505 AC: 1 AN: 197990

Other (OTH) AF: 0.00 AC: 0 AN: 17798

⚠️ 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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.95
PhyloP100		0.18
PromoterAI		0.0080	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: rs557953832; hg19: chr2-149633143;