rs797045455

Variant names:

• chr15-48739006-TTCCTTGGCAAA-AAC
• rs797045455
• NM_001194998.2:c.4365_4376delTTTGCCAAGGAAinsGTT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001194998.2(CEP152):​c.4365_4376delTTTGCCAAGGAAinsGTT​(p.Ser1455_Asn1459delinsArgPhe) variant causes a missense, disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP152 NM_001194998.2 missense, disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.54
• Publications: 0 publications found

Genes affected

CEP152 (HGNC:29298): (centrosomal protein 152) This gene encodes a protein that is thought to be involved with centrosome function. Mutations in this gene have been associated with primary microcephaly (MCPH4). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

CEP152 Gene-Disease associations (from GenCC):

• microcephaly with or without short stature

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Seckel syndrome 5

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• microcephaly 9, primary, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001194998.2.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001194998.2. 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
	CEP152	NM_001194998.2	MANE Select	c.4365_4376delTTTGCCAAGGAAinsGTT	p.Ser1455_Asn1459delinsArgPhe	missense disruptive_inframe_deletion	N/A	NP_001181927.1
	CEP152	NM_014985.4		c.4197_4208delTTTGCCAAGGAAinsGTT	p.Ser1399_Asn1403delinsArgPhe	missense disruptive_inframe_deletion	N/A	NP_055800.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000380950.7	TSL:1 MANE Select	c.4365_4376delTTTGCCAAGGAAinsGTT	p.Ser1455_Asn1459delinsArgPhe	missense disruptive_inframe_deletion	N/A	ENSP00000370337.2
	CEP152	ENST00000399334.7	TSL:1	c.4197_4208delTTTGCCAAGGAAinsGTT	p.Ser1399_Asn1403delinsArgPhe	missense disruptive_inframe_deletion	N/A	ENSP00000382271.3
	CEP152	ENST00000561245.1	TSL:2	n.142+2614_142+2625delTTTGCCAAGGAAinsGTT		intron	N/A	ENSP00000453591.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)
-	1	-	Seckel syndrome 5;C3553886:Microcephaly 9, primary, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5

Splicing

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

Other links and lift over

dbSNP: rs797045455; hg19: chr15-49031203;