rs786205618

Positions:

• chr11-124923383-CAAG-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP5_Moderate

The ENST00000298251.5(HEPACAM):​c.757_759del​(p.Leu253del) variant causes a inframe deletion 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 Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEPACAM ENST00000298251.5 inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.27

Genes affected

HEPACAM (HGNC:26361): (hepatic and glial cell adhesion molecule) The protein encoded by this gene is a single-pass type I membrane protein that localizes to the cytoplasmic side of the cell membrane. The encoded protein acts as a homodimer and is involved in cell motility and cell-matrix interactions. The expression of this gene is downregulated or undetectable in many cancer cell lines, so this may be a tumor suppressor gene. [provided by RefSeq, Jul 2011]

LOC107984406 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000298251.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 11-124923383-CAAG-C is Pathogenic according to our data. Variant chr11-124923383-CAAG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 191275.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPACAM	NM_152722.5	c.757_759del	p.Leu253del	inframe_deletion	4/7	ENST00000298251.5	NP_689935.2
LOC107984406	XR_001748429.3	n.335-20016_335-20014del		intron_variant, non_coding_transcript_variant
HEPACAM	NM_001411043.1	c.757_759del	p.Leu253del	inframe_deletion	4/7		NP_001397972.1
HEPACAM	XM_005271449.3	c.757_759del	p.Leu253del	inframe_deletion	4/7		XP_005271506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEPACAM	ENST00000298251.5	c.757_759del	p.Leu253del	inframe_deletion	4/7	1	NM_152722.5	ENSP00000298251	P1
HEPACAM	ENST00000703807.1	c.757_759del	p.Leu253del	inframe_deletion	4/7			ENSP00000515485

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

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs786205618; hg19: chr11-124793279;