rs762620321

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-62352567-ATTT-A
• chr5-62352567-ATTT-AT
• chr5-62352567-ATTT-ATT
• chr5-62352567-ATTT-ATTTT
• chr5-62352567-ATTT-ATTTTT
• chr5-62352567-ATTT-ATTTTTT

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_335-9delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000446 in 1,119,914 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: KIF2A NM_001098511.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098511.3. 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
	KIF2A	NM_001098511.3	MANE Select	c.335-11_335-9delTTT		intron	N/A	NP_001091981.1	O00139-4
	KIF2A	NM_004520.5		c.335-11_335-9delTTT		intron	N/A	NP_004511.2	O00139-3
	KIF2A	NM_001243953.2		c.335-11_335-9delTTT		intron	N/A	NP_001230882.1	A0A6Q8PFA6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF2A	ENST00000407818.8	TSL:1 MANE Select	c.335-20_335-18delTTT		intron	N/A	ENSP00000385000.3	O00139-4
	KIF2A	ENST00000401507.7	TSL:1	c.335-20_335-18delTTT		intron	N/A	ENSP00000385622.3	O00139-3
	KIF2A	ENST00000381103.7	TSL:1	c.254-20_254-18delTTT		intron	N/A	ENSP00000370493.3	O00139-1

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 148150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000493

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000309 AC: 3 AN: 971764 Hom.: 0 AF XY: 0.00000417 AC XY: 2 AN XY: 479776

⚠️ 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: 20446

American (AMR) AF: 0.00 AC: 0 AN: 18510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16524

East Asian (EAS) AF: 0.00 AC: 0 AN: 24396

South Asian (SAS) AF: 0.00 AC: 0 AN: 52166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36162

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

European-Non Finnish (NFE) AF: 0.00000263 AC: 2 AN: 759142

Other (OTH) AF: 0.0000249 AC: 1 AN: 40084

⚠️ 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 AF: 0.0000135 AC: 2 AN: 148150 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 72066

African (AFR) AF: 0.0000493 AC: 2 AN: 40564

American (AMR) AF: 0.00 AC: 0 AN: 14812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66698

Other (OTH) AF: 0.00 AC: 0 AN: 2026

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs762620321;

hg19: chr5-61648394;