rs199973783

Variant names:

• chr16-29804189-A-T
• rs199973783
• NM_007317.3:c.1677+124A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007317.3(KIF22):​c.1677+124A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 612,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: KIF22 NM_007317.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 0 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

ENSG00000275857 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF22	NM_007317.3	c.1677+124A>T		intron_variant	Intron 11 of 13	ENST00000160827.9	NP_015556.1
KIF22	NM_001256269.2	c.1473+124A>T		intron_variant	Intron 12 of 14		NP_001243198.1
KIF22	NM_001256270.1	c.1473+124A>T		intron_variant	Intron 11 of 13		NP_001243199.1
KIF22	XM_047434094.1	c.*222A>T		downstream_gene_variant			XP_047290050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF22	ENST00000160827.9	c.1677+124A>T		intron_variant	Intron 11 of 13	1	NM_007317.3	ENSP00000160827.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000163 AC: 1 AN: 612870 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 328684

African (AFR) AF: 0.00 AC: 0 AN: 17124

American (AMR) AF: 0.00 AC: 0 AN: 35638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19790

East Asian (EAS) AF: 0.0000296 AC: 1 AN: 33734

South Asian (SAS) AF: 0.00 AC: 0 AN: 65242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3990

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 364550

Other (OTH) AF: 0.00 AC: 0 AN: 32378

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.53
DANN	Benign	0.70
PhyloP100		-2.1
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1

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

Other links and lift over

dbSNP: rs199973783; hg19: chr16-29815510;