1-200606666-A-T

Variant names:

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

Variant summary

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

The NM_014875.3(KIF14):​c.1607+80T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 1,083,846 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: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: KIF14 NM_014875.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 0 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: 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=-0.88).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1083846 Hom.: 0 AF XY: 0.00000360 AC XY: 2 AN XY: 555978

African (AFR) AF: 0.0000386 AC: 1 AN: 25884

American (AMR) AF: 0.00 AC: 0 AN: 43844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23668

East Asian (EAS) AF: 0.00 AC: 0 AN: 37814

South Asian (SAS) AF: 0.00 AC: 0 AN: 78348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5036

European-Non Finnish (NFE) AF: 0.00000130 AC: 1 AN: 770478

Other (OTH) AF: 0.00 AC: 0 AN: 47894

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		-0.0080

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: rs2794410; hg19: chr1-200575794;