15-89633008-TAGGGAGGG-TAGGGAGGGAGGGAGGGAGGGAGGG

Variant names:

• chr15-89633008-T-TAGGGAGGGAGGGAGGG
• rs3840030
• NM_198525.3:c.2719-28_2719-13dupCCCTCCCTCCCTCCCT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_198525.3(KIF7):​c.2719-28_2719-13dupCCCTCCCTCCCTCCCT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (12194 hom., cov: 0)
  • Exomes 𝑓: 0.36 (72605 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF7 NM_198525.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:4
• Conservation: PhyloP100: -0.0130
• Publications: 1 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 -8 ACMG points.

• BP6: Variant 15-89633008-T-TAGGGAGGGAGGGAGGG is Benign according to our data. Variant chr15-89633008-T-TAGGGAGGGAGGGAGGG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 96650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.2719-28_2719-13dupCCCTCCCTCCCTCCCT		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.2719-13_2719-12insCCCTCCCTCCCTCCCT		intron	N/A	ENSP00000377934.3	Q2M1P5
	KIF7	ENST00000696512.1		c.2842-13_2842-12insCCCTCCCTCCCTCCCT		intron	N/A	ENSP00000512678.1	A0A8Q3SIQ8
	KIF7	ENST00000946200.1		c.2731-13_2731-12insCCCTCCCTCCCTCCCT		intron	N/A	ENSP00000616259.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 55279 AN: 129086 Hom.: 12191 Cov.: 0

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.432

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.363 AC: 342631 AN: 942992 Hom.: 72605 Cov.: 22 AF XY: 0.368 AC XY: 177836 AN XY: 482956

African (AFR) AF: 0.257 AC: 6293 AN: 24482

American (AMR) AF: 0.298 AC: 11508 AN: 38630

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 8911 AN: 21310

East Asian (EAS) AF: 0.193 AC: 6833 AN: 35462

South Asian (SAS) AF: 0.374 AC: 27103 AN: 72560

European-Finnish (FIN) AF: 0.432 AC: 16403 AN: 37986

Middle Eastern (MID) AF: 0.254 AC: 1139 AN: 4484

European-Non Finnish (NFE) AF: 0.374 AC: 248349 AN: 664568

Other (OTH) AF: 0.370 AC: 16092 AN: 43510

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.428 AC: 55299 AN: 129190 Hom.: 12194 Cov.: 0 AF XY: 0.422 AC XY: 26324 AN XY: 62352

African (AFR) AF: 0.312 AC: 10996 AN: 35240

American (AMR) AF: 0.383 AC: 4969 AN: 12974

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1515 AN: 3084

East Asian (EAS) AF: 0.244 AC: 1060 AN: 4338

South Asian (SAS) AF: 0.387 AC: 1551 AN: 4010

European-Finnish (FIN) AF: 0.499 AC: 3943 AN: 7902

Middle Eastern (MID) AF: 0.465 AC: 120 AN: 258

European-Non Finnish (NFE) AF: 0.509 AC: 29961 AN: 58848

Other (OTH) AF: 0.431 AC: 762 AN: 1770

Alfa AF: 0.307 Hom.: 1558

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.013
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3840030; hg19: chr15-90176239; COSMIC: COSV51538775; COSMIC: COSV51538775;