Genetic Variant COL5A2:c.2086-13_2086-12dupAA (chr2-189058904-A-ATT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.50

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 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.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000882 (97/1099270) while in subpopulation EAS AF= 0.000722 (24/33226). AF 95% confidence interval is 0.000558. There are 0 homozygotes in gnomad4_exome. There are 47 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 97 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5 link	c.2086-13_2086-12dupAA	intron_variant	Intron 31 of 53	ENST00000374866.9	NP_000384.2	P05997
COL5A2	XM_011510573.4 link	c.1948-13_1948-12dupAA	intron_variant	Intron 34 of 56		XP_011508875.1
COL5A2	XM_047443251.1 link	c.1948-13_1948-12dupAA	intron_variant	Intron 36 of 58		XP_047299207.1
COL5A2	XM_047443252.1 link	c.1948-13_1948-12dupAA	intron_variant	Intron 35 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL5A2	ENST00000374866.9 link	c.2086-12_2086-11insAA	intron_variant	Intron 31 of 53	1	NM_000393.5	ENSP00000364000.3	P05997
COL5A2	ENST00000618828.1 link	c.925-12_925-11insAA	intron_variant	Intron 24 of 46	5		ENSP00000482184.1	A0A087WYX9
COL5A2	ENST00000470524.2 link	n.192-12_192-11insAA	intron_variant	Intron 4 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149582

Hom.:

Cov.:

show subpopulations

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:

AN:

1099270

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

550968

show subpopulations

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:

AN:

149690

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73038

show subpopulations

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

LINK: link

Submissions by phenotype

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Jul 16, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over