rs42526

chr7-94416264-G-Achr7-94416264-G-Cchr7-94416264-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000089.4(COL1A2):c.1765-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 680,802 control chromosomes in the GnomAD database, including 169,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (34060 hom., cov: 33)
  • Exomes 𝑓: 0.71 (135150 hom.)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.90

Genes affected

COL1A2 (HGNC:2198): (collagen type I alpha 2 chain) This gene encodes the pro-alpha2 chain of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIB, recessive Ehlers-Danlos syndrome Classical type, idiopathic osteoporosis, and atypical Marfan syndrome. Symptoms associated with mutations in this gene, however, tend to be less severe than mutations in the gene for the alpha1 chain of type I collagen (COL1A1) reflecting the different role of alpha2 chains in matrix integrity. Three transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-94416264-G-A is Benign according to our data. Variant chr7-94416264-G-A is described in ClinVar as [Benign]. Clinvar id is 1247190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A2	NM_000089.4	c.1765-141G>A		intron_variant		ENST00000297268.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A2	ENST00000297268.11	c.1765-141G>A		intron_variant		1	NM_000089.4	P1
COL1A2	ENST00000473573.5	n.102-141G>A		intron_variant, non_coding_transcript_variant		2
COL1A2	ENST00000488298.5	n.189-141G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100302 AN: 152042 Hom.: 34043 Cov.: 33

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.633

GnomAD4 exome AF: 0.710 AC: 375484 AN: 528642 Hom.: 135150 AF XY: 0.704 AC XY: 194751 AN XY: 276472

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.735

Gnomad4 ASJ exome AF: 0.657

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.751

Gnomad4 NFE exome AF: 0.749

Gnomad4 OTH exome AF: 0.683

GnomAD4 genome AF: 0.660 AC: 100358 AN: 152160 Hom.: 34060 Cov.: 33 AF XY: 0.658 AC XY: 48912 AN XY: 74380

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.630

Alfa AF: 0.627 Hom.: 2178

Bravo AF: 0.652

Asia WGS AF: 0.550 AC: 1911 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	12
Dann	Benign	0.69

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: rs42526; hg19: chr7-94045576;