rs267606717

Variant names:

• chr15-48793359-T-A
• rs267606717
• NM_001194998.2:c.794A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-48793359-T-A
• chr15-48793359-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM5 PP3

The NM_001194998.2(CEP152):​c.794A>T​(p.Gln265Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q265P) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP152 NM_001194998.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.24
• 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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr15-48793359-T-G is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 55.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	NM_001194998.2	MANE Select	c.794A>T	p.Gln265Leu	missense	Exon 7 of 27	NP_001181927.1
	CEP152	NM_014985.4		c.794A>T	p.Gln265Leu	missense	Exon 7 of 26	NP_055800.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000380950.7	TSL:1 MANE Select	c.794A>T	p.Gln265Leu	missense	Exon 7 of 27	ENSP00000370337.2
	CEP152	ENST00000399334.7	TSL:1	c.794A>T	p.Gln265Leu	missense	Exon 7 of 26	ENSP00000382271.3
	CEP152	ENST00000325747.9	TSL:1	c.515A>T	p.Gln172Leu	missense	Exon 6 of 25	ENSP00000321000.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.2
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.25		Loss of disorder (P = 0.0384)
MVP		0.96
MPC		0.39
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.44
gMVP		0.39

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: rs267606717; hg19: chr15-49085556;