chr6-118632503-G-A

Variant names:

• chr6-118632503-G-A
• rs1554234607
• ENST00000360290.7:c.-125C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000360290.7(CEP85L):​c.-125C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a 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: 33)
• Consequence: CEP85L ENST00000360290.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 7.26
• Publications: 0 publications found

Genes affected

CEP85L (HGNC:21638): (centrosomal protein 85 like) The protein encoded by this gene was identified as a breast cancer antigen. Nothing more is known of its function at this time. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

CEP85L Gene-Disease associations (from GenCC):

• lissencephaly 10

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• lissencephaly due to LIS1 mutation

  Inheritance: AD Classification: STRONG Submitted by: Illumina

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360290.7. 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
	CEP85L	NM_001042475.3	MANE Select	c.182C>T	p.Ser61Phe	missense	Exon 2 of 13	NP_001035940.1
	CEP85L	NM_001178035.2		c.191C>T	p.Ser64Phe	missense	Exon 3 of 14	NP_001171506.1
	CEP85L	NM_206921.3		c.182C>T	p.Ser61Phe	missense	Exon 2 of 6	NP_996804.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	ENST00000360290.7	TSL:1	c.-125C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000353434.3
	CEP85L	ENST00000368491.8	TSL:1 MANE Select	c.182C>T	p.Ser61Phe	missense	Exon 2 of 13	ENSP00000357477.3
	CEP85L	ENST00000434604.5	TSL:1	c.191C>T	p.Ser64Phe	missense	Exon 3 of 9	ENSP00000392131.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Lissencephaly (1)
-	1	-	Lissencephaly 10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.32		Gain of sheet (P = 0.0221)
MVP		0.43
MPC		0.46
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.38
gMVP		0.43
Mutation Taster		=59/41	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

Other links and lift over

dbSNP: rs1554234607; hg19: chr6-118953666;