1-200996249-C-T

Variant names:

• chr1-200996249-C-T
• rs750865418
• NM_001252102.2:c.2224G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001252102.2(KIF21B):​c.2224G>A​(p.Glu742Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: KIF21B NM_001252102.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 7.82

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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF21B	NM_001252102.2	c.2224G>A	p.Glu742Lys	missense_variant	Exon 15 of 35	ENST00000461742.7	NP_001239031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF21B	ENST00000461742.7	c.2224G>A	p.Glu742Lys	missense_variant	Exon 15 of 35	1	NM_001252102.2	ENSP00000433808.1
KIF21B	ENST00000422435.2	c.2224G>A	p.Glu742Lys	missense_variant	Exon 15 of 35	1		ENSP00000411831.2
KIF21B	ENST00000332129.6	c.2224G>A	p.Glu742Lys	missense_variant	Exon 15 of 34	1		ENSP00000328494.2
KIF21B	ENST00000360529.9	c.2224G>A	p.Glu742Lys	missense_variant	Exon 15 of 34	1		ENSP00000353724.5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000278 AC: 7 AN: 251484 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461730 Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14 AN XY: 727166

Gnomad4 AFR exome AF: 0.0000299 AC: 1 AN: 33476

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44722

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.000504 AC: 20 AN: 39700

Gnomad4 SAS exome AF: 0.0000116 AC: 1 AN: 86246

Gnomad4 FIN exome AF: 0.0000187 AC: 1 AN: 53418

Gnomad4 NFE exome AF: 8.99e-7 AC: 1 AN: 1112010

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74336

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.000385 AC: 0.000384911 AN: 0.000384911

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00 AC: 0 AN: 0

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Uncertain:1

Feb 05, 2021

New York Genome Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Long QT syndrome Uncertain:1

-

Medical Research Institute, Tokyo Medical and Dental University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	.;.;.;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.8	M;M;M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Benign	0.067	T;T;T;T
Polyphen		0.56	P;.;.;B
Vest4		0.82
MutPred		0.29		Loss of ubiquitination at K746 (P = 0.0213);Loss of ubiquitination at K746 (P = 0.0213);Loss of ubiquitination at K746 (P = 0.0213);Loss of ubiquitination at K746 (P = 0.0213);
MVP		0.67
MPC		0.77
ClinPred		0.65	D
GERP RS		4.8
Varity_R		0.63
gMVP		0.47
Mutation Taster		=56/44	polymorphism

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

Publications

LitVar

Other links and lift over

dbSNP: rs750865418; hg19: chr1-200965377; COSMIC: COSV59754429;