15-89633675-G-T

Variant names:

• chr15-89633675-G-T
• rs78199895
• NM_198525.3:c.2592+11C>A

Variant summary

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

The NM_198525.3(KIF7):​c.2592+11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 1,605,288 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (78 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (65 hom.)
• Consequence: KIF7 NM_198525.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -5.97
• 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 15-89633675-G-T is Benign according to our data. Variant chr15-89633675-G-T is described in ClinVar as Benign. ClinVar VariationId is 263142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

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.2592+11C>A		intron	N/A	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.2592+11C>A		intron	N/A	ENSP00000377934.3	Q2M1P5
	KIF7	ENST00000696512.1		c.2715+11C>A		intron	N/A	ENSP00000512678.1	A0A8Q3SIQ8
	KIF7	ENST00000946200.1		c.2604+11C>A		intron	N/A	ENSP00000616259.1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2760 AN: 152206 Hom.: 78 Cov.: 33

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00570 AC: 1387 AN: 243408 AF XY: 0.00417

Gnomad AFR exome AF: 0.0629

Gnomad AMR exome AF: 0.00629

Gnomad ASJ exome AF: 0.000801

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00112

Gnomad OTH exome AF: 0.00616

GnomAD4 exome AF: 0.00252 AC: 3664 AN: 1452964 Hom.: 65 Cov.: 33 AF XY: 0.00221 AC XY: 1598 AN XY: 723140

African (AFR) AF: 0.0621 AC: 2075 AN: 33392

American (AMR) AF: 0.00751 AC: 335 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.000805 AC: 21 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.000163 AC: 14 AN: 85906

European-Finnish (FIN) AF: 0.0000211 AC: 1 AN: 47396

Middle Eastern (MID) AF: 0.00860 AC: 37 AN: 4304

European-Non Finnish (NFE) AF: 0.000738 AC: 820 AN: 1111478

Other (OTH) AF: 0.00600 AC: 361 AN: 60140

GnomAD4 genome AF: 0.0182 AC: 2769 AN: 152324 Hom.: 78 Cov.: 33 AF XY: 0.0173 AC XY: 1289 AN XY: 74484

African (AFR) AF: 0.0591 AC: 2455 AN: 41566

American (AMR) AF: 0.0139 AC: 213 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68032

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.00874 Hom.: 12

Bravo AF: 0.0217

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Acrocallosal syndrome (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.021
DANN	Benign	0.73
PhyloP100		-6.0
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: rs78199895; hg19: chr15-90176906;