rs2450399

Variant names:

• chr16-29802913-G-A
• rs2450399
• NM_007317.3:c.1425G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-29802913-G-A
• chr16-29802913-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007317.3(KIF22):​c.1425G>A​(p.Val475Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.984 in 1,612,538 control chromosomes in the GnomAD database, including 783,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (65366 hom., cov: 29)
  • Exomes 𝑓: 0.99 (717636 hom.)
• Consequence: KIF22 NM_007317.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.71
• Publications: 18 publications found

Genes affected

KIF22 (HGNC:6391): (kinesin family member 22) The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. The C-terminal half of this protein has been shown to bind DNA. Studies with the Xenopus homolog suggests its essential role in metaphase chromosome alignment and maintenance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

KIF22 Gene-Disease associations (from GenCC):

• spondyloepimetaphyseal dysplasia with multiple dislocations

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 16-29802913-G-A is Benign according to our data. Variant chr16-29802913-G-A is described in ClinVar as Benign. ClinVar VariationId is 803248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007317.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF22	NM_007317.3	MANE Select	c.1425G>A	p.Val475Val	synonymous	Exon 9 of 14	NP_015556.1
	KIF22	NM_001256269.2		c.1221G>A	p.Val407Val	synonymous	Exon 10 of 15	NP_001243198.1
	KIF22	NM_001256270.1		c.1221G>A	p.Val407Val	synonymous	Exon 9 of 14	NP_001243199.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF22	ENST00000160827.9	TSL:1 MANE Select	c.1425G>A	p.Val475Val	synonymous	Exon 9 of 14	ENSP00000160827.5
	KIF22	ENST00000569382.3	TSL:5	c.1425G>A	p.Val475Val	synonymous	Exon 9 of 14	ENSP00000456165.3
	KIF22	ENST00000689660.1		c.1377G>A	p.Val459Val	synonymous	Exon 9 of 14	ENSP00000509285.1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139706 AN: 151920 Hom.: 65321 Cov.: 29

Gnomad AFR AF: 0.730

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.984

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.996

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.948

GnomAD2 exomes AF: 0.974 AC: 243375 AN: 249880 AF XY: 0.980

Gnomad AFR exome AF: 0.724

Gnomad AMR exome AF: 0.986

Gnomad ASJ exome AF: 0.989

Gnomad EAS exome AF: 0.934

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.986

GnomAD4 exome AF: 0.990 AC: 1446473 AN: 1460500 Hom.: 717636 Cov.: 49 AF XY: 0.992 AC XY: 720503 AN XY: 726556

African (AFR) AF: 0.726 AC: 24248 AN: 33396

American (AMR) AF: 0.985 AC: 43739 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 25783 AN: 26096

East Asian (EAS) AF: 0.953 AC: 37779 AN: 39634

South Asian (SAS) AF: 0.998 AC: 85761 AN: 85892

European-Finnish (FIN) AF: 1.00 AC: 53400 AN: 53400

Middle Eastern (MID) AF: 0.991 AC: 5708 AN: 5760

European-Non Finnish (NFE) AF: 0.999 AC: 1111002 AN: 1111566

Other (OTH) AF: 0.979 AC: 59053 AN: 60344

GnomAD4 genome AF: 0.920 AC: 139805 AN: 152038 Hom.: 65366 Cov.: 29 AF XY: 0.921 AC XY: 68450 AN XY: 74322

African (AFR) AF: 0.730 AC: 30196 AN: 41380

American (AMR) AF: 0.970 AC: 14820 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.984 AC: 3416 AN: 3472

East Asian (EAS) AF: 0.935 AC: 4811 AN: 5146

South Asian (SAS) AF: 0.997 AC: 4813 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10604 AN: 10604

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67954 AN: 68020

Other (OTH) AF: 0.948 AC: 1991 AN: 2100

Alfa AF: 0.961 Hom.: 30778

Bravo AF: 0.907

Asia WGS AF: 0.960 AC: 3339 AN: 3478

EpiCase AF: 0.998

EpiControl AF: 0.999

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Spondyloepimetaphyseal dysplasia with multiple dislocations (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.9
DANN	Benign	0.59
PhyloP100		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=299/1	polymorphism (auto)

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: rs2450399; hg19: chr16-29814234; COSMIC: COSV108033007; COSMIC: COSV108033007;