7-94395819-TAA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000089.4(COL1A2):c.70+719_70+720del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 152,254 control chromosomes in the GnomAD database, including 35 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.017 (35 hom., cov: 32)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.720

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 -16 ACMG points.

• BP6: Variant 7-94395819-TAA-T is Benign according to our data. Variant chr7-94395819-TAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 671158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0167 (2541/152254) while in subpopulation SAS AF= 0.0344 (166/4828). AF 95% confidence interval is 0.0301. There are 35 homozygotes in gnomad4. There are 1263 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 35 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL1A2	NM_000089.4	c.70+719_70+720del		intron_variant		ENST00000297268.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL1A2	ENST00000297268.11	c.70+719_70+720del		intron_variant		1	NM_000089.4	P1

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2540 AN: 152136 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0902

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0341

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0218

Gnomad OTH AF: 0.0211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0167 AC: 2541 AN: 152254 Hom.: 35 Cov.: 32 AF XY: 0.0170 AC XY: 1263 AN XY: 74444

Gnomad4 AFR AF: 0.00390

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.0902

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.0154

Gnomad4 NFE AF: 0.0218

Gnomad4 OTH AF: 0.0209

Alfa AF: 0.0189 Hom.: 4

Bravo AF: 0.0154

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 21, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs201691876; hg19: chr7-94025131;