NM_001098511.3:c.335-9dupT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001098511.3(KIF2A):​c.335-9dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,058,038 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.018 (1 hom.)
• Consequence: KIF2A NM_001098511.3 splice_region, intron
• Clinical Significance: Likely 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 -6 ACMG points.

• BP6: Variant 5-62352567-A-AT is Benign according to our data. Variant chr5-62352567-A-AT is described in ClinVar as Likely_benign. ClinVar VariationId is 445895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 70 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 70 AN: 148094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000338

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.000730

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000570

Gnomad OTH AF: 0.000494

GnomAD2 exomes AF: 0.0393 AC: 1806 AN: 45996 AF XY: 0.0422

Gnomad AFR exome AF: 0.0334

Gnomad AMR exome AF: 0.0579

Gnomad ASJ exome AF: 0.0532

Gnomad EAS exome AF: 0.0519

Gnomad FIN exome AF: 0.0108

Gnomad NFE exome AF: 0.0381

Gnomad OTH exome AF: 0.0387

GnomAD4 exome AF: 0.0177 AC: 16106 AN: 909874 Hom.: 1 Cov.: 17 AF XY: 0.0178 AC XY: 7998 AN XY: 449278

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

African (AFR) AF: 0.0170 AC: 326 AN: 19216

American (AMR) AF: 0.0216 AC: 383 AN: 17760

Ashkenazi Jewish (ASJ) AF: 0.0174 AC: 268 AN: 15446

East Asian (EAS) AF: 0.0152 AC: 346 AN: 22802

South Asian (SAS) AF: 0.0251 AC: 1242 AN: 49510

European-Finnish (FIN) AF: 0.0113 AC: 390 AN: 34554

Middle Eastern (MID) AF: 0.00887 AC: 37 AN: 4172

European-Non Finnish (NFE) AF: 0.0175 AC: 12413 AN: 708894

Other (OTH) AF: 0.0187 AC: 701 AN: 37520

⚠️ 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: 0.000472 AC: 70 AN: 148164 Hom.: 0 Cov.: 32 AF XY: 0.000555 AC XY: 40 AN XY: 72114

African (AFR) AF: 0.000369 AC: 15 AN: 40650

American (AMR) AF: 0.000337 AC: 5 AN: 14826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.000393 AC: 2 AN: 5094

South Asian (SAS) AF: 0.000426 AC: 2 AN: 4696

European-Finnish (FIN) AF: 0.000730 AC: 7 AN: 9590

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

European-Non Finnish (NFE) AF: 0.000570 AC: 38 AN: 66662

Other (OTH) AF: 0.000490 AC: 1 AN: 2040

Alfa AF: 0.0120 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 03, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely 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;