5-62347942-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001098511.3(KIF2A):c.160-106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 1,269,498 control chromosomes in the GnomAD database, including 3,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (324 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3042 hom.)
• Consequence: KIF2A NM_001098511.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0220

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]

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-62347942-G-A is Benign according to our data. Variant chr5-62347942-G-A is described in ClinVar as [Benign]. Clinvar id is 1271265.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF2A	NM_001098511.3	c.160-106G>A		intron_variant		ENST00000407818.8
KIF2A	NM_001243952.2	c.79-106G>A		intron_variant
KIF2A	NM_001243953.2	c.160-106G>A		intron_variant
KIF2A	NM_004520.5	c.160-106G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF2A	ENST00000407818.8	c.160-106G>A		intron_variant		1	NM_001098511.3	A1

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8515 AN: 151928 Hom.: 323 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0788

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0370

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0591

GnomAD4 exome AF: 0.0701 AC: 78373 AN: 1117452 Hom.: 3042 AF XY: 0.0689 AC XY: 38351 AN XY: 556432

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.0306

Gnomad4 ASJ exome AF: 0.0758

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.0321

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.0725

Gnomad4 OTH exome AF: 0.0676

GnomAD4 genome AF: 0.0560 AC: 8514 AN: 152046 Hom.: 324 Cov.: 32 AF XY: 0.0567 AC XY: 4216 AN XY: 74326

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0425

Gnomad4 ASJ AF: 0.0788

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0364

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.0585

Alfa AF: 0.0636 Hom.: 47

Bravo AF: 0.0500

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.2
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs3776614; hg19: chr5-61643769; COSMIC: COSV66945333;