1-200974857-G-GA

Variant names:

• chr1-200974857-G-GA
• NM_001252102.2:c.4670_4671insT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001252102.2(KIF21B):​c.4670_4671insT​(p.Met1559HisfsTer24) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF21B NM_001252102.2 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02
• Publications: 0 publications found

Genes affected

KIF21B (HGNC:29442): (kinesin family member 21B) This gene encodes a member of the kinesin superfamily. Kinesins are ATP-dependent microtubule-based motor proteins that are involved in the intracellular transport of membranous organelles. Single nucleotide polymorphisms in this gene are associated with inflammatory bowel disease and multiple sclerosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252102.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF21B	NM_001252102.2	MANE Select	c.4670_4671insT	p.Met1559HisfsTer24	frameshift	Exon 34 of 35	NP_001239031.1	O75037-4
	KIF21B	NM_001252100.2		c.4670_4671insT	p.Met1559HisfsTer24	frameshift	Exon 34 of 35	NP_001239029.1	O75037-1
	KIF21B	NM_017596.4		c.4631_4632insT	p.Met1546HisfsTer24	frameshift	Exon 33 of 34	NP_060066.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF21B	ENST00000461742.7	TSL:1 MANE Select	c.4670_4671insT	p.Met1559HisfsTer24	frameshift	Exon 34 of 35	ENSP00000433808.1	O75037-4
	KIF21B	ENST00000422435.2	TSL:1	c.4670_4671insT	p.Met1559HisfsTer24	frameshift	Exon 34 of 35	ENSP00000411831.2	O75037-1
	KIF21B	ENST00000332129.6	TSL:1	c.4631_4632insT	p.Met1546HisfsTer24	frameshift	Exon 33 of 34	ENSP00000328494.2	O75037-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Neurodevelopmental disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

hg19: chr1-200943985;