5-62352567-ATTT-ATTTTTT

Variant names:

• chr5-62352567-A-ATTT
• rs762620321
• NM_001098511.3:c.335-11_335-9dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001098511.3(KIF2A):​c.335-11_335-9dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000309 in 971,834 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF2A	NM_001098511.3	c.335-11_335-9dupTTT		splice_region_variant, intron_variant	Intron 4 of 20	ENST00000407818.8	NP_001091981.1
KIF2A	NM_004520.5	c.335-11_335-9dupTTT		splice_region_variant, intron_variant	Intron 4 of 19		NP_004511.2
KIF2A	NM_001243953.2	c.335-11_335-9dupTTT		splice_region_variant, intron_variant	Intron 4 of 19		NP_001230882.1
KIF2A	NM_001243952.2	c.254-11_254-9dupTTT		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_335-20insTTT		intron_variant	Intron 4 of 20	1	NM_001098511.3	ENSP00000385000.3
ENSG00000288643	ENST00000509663.2	n.64+46031_64+46032insTTT		intron_variant	Intron 1 of 5	3		ENSP00000502199.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000309 AC: 3 AN: 971834 Hom.: 0 Cov.: 17 AF XY: 0.00000417 AC XY: 2 AN XY: 479824

⚠️ 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: 20448

American (AMR) AF: 0.000108 AC: 2 AN: 18508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16522

East Asian (EAS) AF: 0.00 AC: 0 AN: 24394

South Asian (SAS) AF: 0.0000192 AC: 1 AN: 52166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4334

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 759208

Other (OTH) AF: 0.00 AC: 0 AN: 40086

⚠️ 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;