KIF7 p.Glu969Asp

Variant names:

• chr15-89631699-C-A
• NM_198525.3:c.2907G>T
• KIF7 p.Glu969Asp

Your query was ambiguous. Multiple possible variants found:

• chr15-89631699-C-A
• chr15-89631699-C-G

Variant summary

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

The NM_198525.3(KIF7):​c.2907G>T​(p.Glu969Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. E969E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF7 NM_198525.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364
• Publications: 0 publications found

Genes affected

KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]

KIF7 Gene-Disease associations (from GenCC):

• acrocallosal syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• hydrolethalus syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• hydrolethalus syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• multiple epiphyseal dysplasia, Al-Gazali type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 (MetaRNN=0.051559538).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198525.3. 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
	KIF7	NM_198525.3	MANE Select	c.2907G>T	p.Glu969Asp	missense	Exon 15 of 19	NP_940927.2	Q2M1P5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF7	ENST00000394412.8	TSL:5 MANE Select	c.2907G>T	p.Glu969Asp	missense	Exon 15 of 19	ENSP00000377934.3	Q2M1P5
	KIF7	ENST00000696512.1		c.3030G>T	p.Glu1010Asp	missense	Exon 15 of 19	ENSP00000512678.1	A0A8Q3SIQ8
	KIF7	ENST00000946200.1		c.2919G>T	p.Glu973Asp	missense	Exon 15 of 19	ENSP00000616259.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1401000 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 691116

African (AFR) AF: 0.00 AC: 0 AN: 31726

American (AMR) AF: 0.00 AC: 0 AN: 36590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35942

South Asian (SAS) AF: 0.00 AC: 0 AN: 79574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079344

Other (OTH) AF: 0.00 AC: 0 AN: 58022

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.76	N
PhyloP100		0.36
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.080
Sift	Benign	0.22	T
Sift4G	Benign	0.26	T
Varity_R		0.053
gMVP		0.10
Mutation Taster		=96/4	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-90174930;