chr2-189061585-G-A

Variant names:

• chr2-189061585-G-A
• rs904166744
• NM_000393.5:c.2008C>T

Variant summary

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

The NM_000393.5(COL5A2):​c.2008C>T​(p.Pro670Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P670T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL5A2 NM_000393.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.26
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome, classic type

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Ehlers-Danlos syndrome, classic type, 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.2008C>T	p.Pro670Ser	missense_variant	Exon 30 of 54	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.1870C>T	p.Pro624Ser	missense_variant	Exon 33 of 57		XP_011508875.1
COL5A2	XM_047443251.1	c.1870C>T	p.Pro624Ser	missense_variant	Exon 35 of 59		XP_047299207.1
COL5A2	XM_047443252.1	c.1870C>T	p.Pro624Ser	missense_variant	Exon 34 of 58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.2008C>T	p.Pro670Ser	missense_variant	Exon 30 of 54	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.847C>T	p.Pro283Ser	missense_variant	Exon 23 of 47	5		ENSP00000482184.1
COL5A2	ENST00000470524.2	n.114C>T		non_coding_transcript_exon_variant	Exon 3 of 8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D;T;D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Benign	1.6	L;.;L
PhyloP100		7.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.2	D;.;.
REVEL	Pathogenic	0.68
Sift	Benign	0.090	T;.;.
Sift4G	Benign	0.063	T;T;.
Polyphen		0.85	P;.;P
Vest4		0.44
MutPred		0.38		Gain of phosphorylation at P670 (P = 0.0101);.;Gain of phosphorylation at P670 (P = 0.0101);
MVP		0.60
MPC		0.26
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.27
gMVP		0.42
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs904166744; hg19: chr2-189926311;