chr9-134834981-TGGACGCCGA-T

Position:

• chr9-134834981-TGGACGCCGA-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PM4 PP3 PP5_Moderate

The NM_000093.5(COL5A1):​c.5150_5158del​(p.Asp1717_Glu1719del) 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 (★). Synonymous variant affecting the same amino acid position (i.e. V1716V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL5A1 NM_000093.5 inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.78

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

LOC101448202 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000093.5.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 9-134834981-TGGACGCCGA-T is Pathogenic according to our data. Variant chr9-134834981-TGGACGCCGA-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 523326.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A1	NM_000093.5	c.5150_5158del	p.Asp1717_Glu1719del	inframe_deletion	65/66	ENST00000371817.8
LOC101448202	NR_103451.2	n.71-14781_71-14773del		intron_variant, non_coding_transcript_variant
COL5A1	NM_001278074.1	c.5150_5158del	p.Asp1717_Glu1719del	inframe_deletion	65/66
COL5A1	XM_017014266.3			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A1	ENST00000371817.8	c.5150_5158del	p.Asp1717_Glu1719del	inframe_deletion	65/66	1	NM_000093.5	P4
COL5A1	ENST00000371820.4	c.5150_5158del	p.Asp1717_Glu1719del	inframe_deletion	65/66	2		A2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atrophic scars;C0241074:Hyperextensible skin;C1844820:Joint hypermobility;C1851828:Cigarette-paper scars;C4025260:Large joint dislocations Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 01, 2017

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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: rs1554726245; hg19: chr9-137726827;