rs587779612

chr2-188994036-AGGGCCCTCCTGGGATTAA-ACCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP3 PP5

The NM_000090.4(COL3A1):c.1150-1_1166delinsCCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC variant causes a splice acceptor, coding sequence 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL3A1 NM_000090.4 splice_acceptor, coding_sequence
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.55

Genes affected

COL3A1 (HGNC:2201): (collagen type III alpha 1 chain) This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome type IV, and with aortic and arterial aneurysms. [provided by R. Dalgleish, Feb 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.0049988637 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 2-188994037-GGGCCCTCCTGGGATTAA-CCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC is Pathogenic according to our data. Variant chr2-188994037-GGGCCCTCCTGGGATTAA-CCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC is described in ClinVar as [Pathogenic]. Clinvar id is 101332.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL3A1	NM_000090.4	c.1150-1_1166delinsCCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC		splice_acceptor_variant, coding_sequence_variant	17/51	ENST00000304636.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL3A1	ENST00000304636.9	c.1150-1_1166delinsCCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC		splice_acceptor_variant, coding_sequence_variant	17/51	1	NM_000090.4	P1
COL3A1	ENST00000450867.2	c.1051-1_1067delinsCCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC		splice_acceptor_variant, coding_sequence_variant	16/50	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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ehlers-Danlos syndrome, type 4 Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Collagen Diagnostic Laboratory, University of Washington

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587779612; hg19: chr2-189858763;