2-189058904-A-ATT

Position:

• chr2-189058904-A-ATT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000393.5(COL5A2):​c.2086-13_2086-12dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.50

Genes affected

COL5A2 (HGNC:2210): (collagen type V alpha 2 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. Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. [provided by RefSeq, Jul 2008]

COL5A2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-189058904-A-ATT is Benign according to our data. Variant chr2-189058904-A-ATT is described in ClinVar as [Benign]. Clinvar id is 2897007.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 97 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.2086-13_2086-12dupAA		intron_variant		ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.1948-13_1948-12dupAA		intron_variant			XP_011508875.1
COL5A2	XM_047443251.1	c.1948-13_1948-12dupAA		intron_variant			XP_047299207.1
COL5A2	XM_047443252.1	c.1948-13_1948-12dupAA		intron_variant			XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.2086-13_2086-12dupAA		intron_variant		1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.925-13_925-12dupAA		intron_variant		5		ENSP00000482184.1
COL5A2	ENST00000470524.2	n.192-13_192-12dupAA		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149582 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000882 AC: 97 AN: 1099270 Hom.: 0 Cov.: 0 AF XY: 0.0000853 AC XY: 47 AN XY: 550968

Gnomad4 AFR exome AF: 0.000107

Gnomad4 AMR exome AF: 0.000209

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000722

Gnomad4 SAS exome AF: 0.000716

Gnomad4 FIN exome AF: 0.0000455

Gnomad4 NFE exome AF: 0.00000736

Gnomad4 OTH exome AF: 0.0000867

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149690 Hom.: 0 Cov.: 0 AF XY: 0.0000137 AC XY: 1 AN XY: 73038

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ehlers-Danlos syndrome, classic type, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 16, 2023

- -

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: rs5837121; hg19: chr2-189923630;