5-62306509-A-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_001098511.3(KIF2A):c.37A>G(p.Ile13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,392,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KIF2A NM_001098511.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.62

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36264217).
• BP6: Variant 5-62306509-A-G is Benign according to our data. Variant chr5-62306509-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2793430.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF2A	NM_001098511.3	c.37A>G	p.Ile13Val	missense_variant	1/21	ENST00000407818.8
KIF2A	NM_004520.5	c.37A>G	p.Ile13Val	missense_variant	1/20
KIF2A	NM_001243953.2	c.37A>G	p.Ile13Val	missense_variant	1/20
KIF2A	NM_001243952.2	c.-248A>G		5_prime_UTR_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF2A	ENST00000407818.8	c.37A>G	p.Ile13Val	missense_variant	1/21	1	NM_001098511.3	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1392772 Hom.: 0 Cov.: 32 AF XY: 0.00000291 AC XY: 2 AN XY: 686942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.025	T;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.79	N;.;N
MutationTaster	Benign	0.77	D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.090	N;N;N
REVEL	Benign	0.045
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.17
MutPred		0.38		Gain of MoRF binding (P = 0.1039);Gain of MoRF binding (P = 0.1039);Gain of MoRF binding (P = 0.1039);
MVP		0.70
MPC		0.72
ClinPred		0.44	T
GERP RS		4.2
Varity_R		0.13
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-61602336;