5-62352567-ATTT-ATTTTT

Variant names:

• chr5-62352567-A-ATT
• rs762620321
• NM_001098511.3:c.335-10_335-9dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001098511.3(KIF2A):​c.335-10_335-9dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 970,640 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: KIF2A NM_001098511.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 0 publications found

Genes affected

KIF2A (HGNC:6318): (kinesin family member 2A) The protein encoded by this gene is a plus end-directed motor required for normal mitotic progression. The encoded protein is required for normal spindle activity during mitosis and is necessary for normal brain development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000288643 (HGNC:):

DIMT1 (HGNC:30217): (DIM1 rRNA methyltransferase and ribosome maturation factor) The protein encoded by this gene is a methyltransferase that is responsible for dimethylation of adjacent adenosines near the 18S rRNA decoding site. The encoded protein is essential for ribosome biogenesis, although its catalytic activity is not involved in the process. The yeast ortholog of this protein functions in the cytoplasm while this protein functions in the nucleus. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF2A	NM_001098511.3	c.335-10_335-9dupTT		splice_region_variant, intron_variant	Intron 4 of 20	ENST00000407818.8	NP_001091981.1
KIF2A	NM_004520.5	c.335-10_335-9dupTT		splice_region_variant, intron_variant	Intron 4 of 19		NP_004511.2
KIF2A	NM_001243953.2	c.335-10_335-9dupTT		splice_region_variant, intron_variant	Intron 4 of 19		NP_001230882.1
KIF2A	NM_001243952.2	c.254-10_254-9dupTT		splice_region_variant, intron_variant	Intron 5 of 20		NP_001230881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818.8	c.335-21_335-20insTT		intron_variant	Intron 4 of 20	1	NM_001098511.3	ENSP00000385000.3
ENSG00000288643	ENST00000509663.2	n.64+46031_64+46032insTT		intron_variant	Intron 1 of 5	3		ENSP00000502199.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000435 AC: 20 AN: 45996 AF XY: 0.000391

Gnomad AFR exome AF: 0.000982

Gnomad AMR exome AF: 0.000994

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.000135

Gnomad NFE exome AF: 0.000209

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000731 AC: 71 AN: 970640 Hom.: 0 Cov.: 17 AF XY: 0.0000522 AC XY: 25 AN XY: 479220

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

African (AFR) AF: 0.000196 AC: 4 AN: 20420

American (AMR) AF: 0.000162 AC: 3 AN: 18486

Ashkenazi Jewish (ASJ) AF: 0.000182 AC: 3 AN: 16504

East Asian (EAS) AF: 0.0000410 AC: 1 AN: 24370

South Asian (SAS) AF: 0.000134 AC: 7 AN: 52060

European-Finnish (FIN) AF: 0.0000553 AC: 2 AN: 36154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4332

European-Non Finnish (NFE) AF: 0.0000659 AC: 50 AN: 758274

Other (OTH) AF: 0.0000250 AC: 1 AN: 40040

⚠️ 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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs762620321; hg19: chr5-61648394;