NM_000393.5:c.3343G>T

Variant names:

• chr2-189045199-C-A
• rs748601646
• NM_000393.5:c.3343G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000393.5(COL5A2):​c.3343G>T​(p.Ala1115Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,453,728 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COL5A2 NM_000393.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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.3343G>T	p.Ala1115Ser	missense_variant	Exon 47 of 54	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.3205G>T	p.Ala1069Ser	missense_variant	Exon 50 of 57		XP_011508875.1
COL5A2	XM_047443251.1	c.3205G>T	p.Ala1069Ser	missense_variant	Exon 52 of 59		XP_047299207.1
COL5A2	XM_047443252.1	c.3205G>T	p.Ala1069Ser	missense_variant	Exon 51 of 58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.3343G>T	p.Ala1115Ser	missense_variant	Exon 47 of 54	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.2182G>T	p.Ala728Ser	missense_variant	Exon 40 of 47	5		ENSP00000482184.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246346 Hom.: 0 AF XY: 0.00000748 AC XY: 1 AN XY: 133750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453728 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000237

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;T;D
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Uncertain	0.0022	D
MutationAssessor	Benign	1.3	L;.;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.7	N;.;.
REVEL	Uncertain	0.30
Sift	Benign	0.088	T;.;.
Sift4G	Benign	0.30	T;T;.
Polyphen		0.76	P;.;P
Vest4		0.41
MutPred		0.27		Gain of phosphorylation at A1115 (P = 0.0019);.;Gain of phosphorylation at A1115 (P = 0.0019);
MVP		0.75
MPC		0.24
ClinPred		0.84	D
GERP RS		4.8
Varity_R		0.078
gMVP		0.076

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

Publications

LitVar

Other links and lift over

dbSNP: rs748601646; hg19: chr2-189909925;