NM_000393.5:c.1292A>C

Variant names:

• chr2-189068236-T-G
• NM_000393.5:c.1292A>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000393.5(COL5A2):​c.1292A>C​(p.Lys431Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COL5A2 NM_000393.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.1292A>C	p.Lys431Thr	missense_variant	Exon 20 of 54	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.1154A>C	p.Lys385Thr	missense_variant	Exon 23 of 57		XP_011508875.1
COL5A2	XM_047443251.1	c.1154A>C	p.Lys385Thr	missense_variant	Exon 25 of 59		XP_047299207.1
COL5A2	XM_047443252.1	c.1154A>C	p.Lys385Thr	missense_variant	Exon 24 of 58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.1292A>C	p.Lys431Thr	missense_variant	Exon 20 of 54	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.359-1803A>C		intron_variant	Intron 15 of 46	5		ENSP00000482184.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461666 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727164

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

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	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D;D
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-4.5	D;.
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0030	D;.
Polyphen		0.85	P;P
Vest4		0.70
MutPred		0.52		Loss of methylation at K431 (P = 8e-04);Loss of methylation at K431 (P = 8e-04);
MVP		0.83
MPC		0.99
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.51
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-189932962;