chr5-62352567-AT-A

Variant names:

• chr5-62352567-AT-A
• rs762620321
• NM_001098511.3:c.335-9delT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001098511.3(KIF2A):​c.335-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 929,956 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.067 (0 hom.)
• Consequence: KIF2A NM_001098511.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 5-62352567-AT-A is Benign according to our data. Variant chr5-62352567-AT-A is described in ClinVar as Benign. ClinVar VariationId is 1599889.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000311 AC: 46 AN: 147980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000419

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000338

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000210

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.141 AC: 6506 AN: 45996 AF XY: 0.162

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.184

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.134

Gnomad FIN exome AF: 0.0536

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.0674 AC: 52706 AN: 781906 Hom.: 0 Cov.: 17 AF XY: 0.0690 AC XY: 26485 AN XY: 384102

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

African (AFR) AF: 0.0666 AC: 1092 AN: 16398

American (AMR) AF: 0.0963 AC: 1497 AN: 15548

Ashkenazi Jewish (ASJ) AF: 0.0950 AC: 1211 AN: 12742

East Asian (EAS) AF: 0.0857 AC: 1560 AN: 18210

South Asian (SAS) AF: 0.0921 AC: 4045 AN: 43906

European-Finnish (FIN) AF: 0.0618 AC: 1700 AN: 27510

Middle Eastern (MID) AF: 0.0429 AC: 160 AN: 3730

European-Non Finnish (NFE) AF: 0.0639 AC: 39119 AN: 612226

Other (OTH) AF: 0.0734 AC: 2322 AN: 31636

⚠️ 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: 0.000317 AC: 47 AN: 148050 Hom.: 0 Cov.: 32 AF XY: 0.000375 AC XY: 27 AN XY: 72064

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

African (AFR) AF: 0.000443 AC: 18 AN: 40640

American (AMR) AF: 0.000338 AC: 5 AN: 14810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4694

European-Finnish (FIN) AF: 0.00105 AC: 10 AN: 9554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000210 AC: 14 AN: 66614

Other (OTH) AF: 0.00 AC: 0 AN: 2040

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000697699), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0385 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.33
Mutation Taster		=100/0	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: rs762620321; hg19: chr5-61648394; COSMIC: COSV66945163; COSMIC: COSV66945163;