rs2794410

Variant names:

• chr1-200606666-A-G
• rs2794410
• NM_014875.3:c.1607+80T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-200606666-A-G
• chr1-200606666-A-T

Variant summary

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

The NM_014875.3(KIF14):​c.1607+80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,233,608 control chromosomes in the GnomAD database, including 71,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8812 hom., cov: 31)
  • Exomes 𝑓: 0.33 (62450 hom.)
• Consequence: KIF14 NM_014875.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00800
• Publications: 12 publications found

Genes affected

KIF14 (HGNC:19181): (kinesin family member 14) This gene encodes a member of the kinesin-3 superfamily of microtubule motor proteins. These proteins are involved in numerous processes including vesicle transport, chromosome segregation, mitotic spindle formation, and cytokinesis. In human HeLa-S3 and 293T cells, this protein is localized to the cytoplasm during interphase, to the spindle poles and spindle microtubules during mitosis, and to the midbody during cytokinesis. An internal motor domain displays microtubule-dependent ATPase activity, consistent with its function as a microtubule motor protein. Knockdown of this gene results in failed cytokinesis with endoreplication, which results in multinucleated cells. This gene has been identified as a likely oncogene in breast, lung and ovarian cancers, as well as retinoblastomas and gliomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

KIF14 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
• lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• microcephaly 20, primary, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-200606666-A-G is Benign according to our data. Variant chr1-200606666-A-G is described in ClinVar as [Benign]. Clinvar id is 1226287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF14	NM_014875.3	c.1607+80T>C		intron_variant	Intron 6 of 29	ENST00000367350.5	NP_055690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF14	ENST00000367350.5	c.1607+80T>C		intron_variant	Intron 6 of 29	2	NM_014875.3	ENSP00000356319.4
KIF14	ENST00000614960.4	c.1607+80T>C		intron_variant	Intron 5 of 28	1		ENSP00000483069.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50993 AN: 151860 Hom.: 8807 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.334 AC: 360768 AN: 1081630 Hom.: 62450 AF XY: 0.330 AC XY: 183282 AN XY: 554850

African (AFR) AF: 0.348 AC: 9003 AN: 25850

American (AMR) AF: 0.300 AC: 13149 AN: 43820

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 5844 AN: 23648

East Asian (EAS) AF: 0.155 AC: 5879 AN: 37810

South Asian (SAS) AF: 0.250 AC: 19604 AN: 78278

European-Finnish (FIN) AF: 0.451 AC: 22938 AN: 50816

Middle Eastern (MID) AF: 0.259 AC: 1303 AN: 5030

European-Non Finnish (NFE) AF: 0.348 AC: 267673 AN: 768558

Other (OTH) AF: 0.322 AC: 15375 AN: 47820

GnomAD4 genome AF: 0.336 AC: 51027 AN: 151978 Hom.: 8812 Cov.: 31 AF XY: 0.335 AC XY: 24920 AN XY: 74292

African (AFR) AF: 0.354 AC: 14675 AN: 41464

American (AMR) AF: 0.304 AC: 4635 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3470

East Asian (EAS) AF: 0.165 AC: 853 AN: 5172

South Asian (SAS) AF: 0.247 AC: 1189 AN: 4822

European-Finnish (FIN) AF: 0.443 AC: 4659 AN: 10528

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23152 AN: 67940

Other (OTH) AF: 0.289 AC: 611 AN: 2112

Alfa AF: 0.334 Hom.: 30433

Bravo AF: 0.327

Asia WGS AF: 0.206 AC: 719 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		-0.0080
Mutation Taster		=100/0	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: rs2794410; hg19: chr1-200575794; COSMIC: COSV66260571;