6-118481910-AT-ATTTTTTTT

Variant names:

• chr6-118481910-A-ATTTTTTT
• rs1554203314
• NM_001042475.3:c.1607_1613dupAAAAAAA

Variant summary

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

The NM_001042475.3(CEP85L):​c.1607_1613dupAAAAAAA​(p.Asn538LysfsTer4) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEP85L NM_001042475.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12
• 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• lissencephaly due to LIS1 mutation

  Inheritance: AD Classification: STRONG Submitted by: Illumina

ENSG00000303332 (HGNC:):

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: NM_001042475.3. 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
	CEP85L	NM_001042475.3	MANE Select	c.1607_1613dupAAAAAAA	p.Asn538LysfsTer4	frameshift	Exon 8 of 13	NP_001035940.1	Q5SZL2-1
	CEP85L	NM_001178035.2		c.1616_1622dupAAAAAAA	p.Asn541LysfsTer4	frameshift	Exon 9 of 14	NP_001171506.1	Q5SZL2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	ENST00000368491.8	TSL:1 MANE Select	c.1607_1613dupAAAAAAA	p.Asn538LysfsTer4	frameshift	Exon 8 of 13	ENSP00000357477.3	Q5SZL2-1
	CEP85L	ENST00000434604.5	TSL:1	c.1616_1622dupAAAAAAA	p.Asn541LysfsTer4	frameshift	Exon 9 of 9	ENSP00000392131.1	A2A3P3
	CEP85L	ENST00000368488.9	TSL:5	c.1616_1622dupAAAAAAA	p.Asn541LysfsTer4	frameshift	Exon 9 of 14	ENSP00000357474.5	Q5SZL2-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000660 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

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

Other links and lift over

dbSNP: rs1554203314; hg19: chr6-118803073;