4-79901827-G-C

Variant summary

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

The NM_058172.6(ANTXR2):c.*5602C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 151,988 control chromosomes in the GnomAD database, including 2,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (2438 hom., cov: 30)
  • Exomes 𝑓: 0.082 (1 hom.)
• Consequence: ANTXR2 NM_058172.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.365

Genes affected

ANTXR2 (HGNC:21732): (ANTXR cell adhesion molecule 2) This gene encodes a receptor for anthrax toxin. The protein binds to collagen IV and laminin, suggesting that it may be involved in extracellular matrix adhesion. Mutations in this gene cause juvenile hyaline fibromatosis and infantile systemic hyalinosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 4-79901827-G-C is Benign according to our data. Variant chr4-79901827-G-C is described in ClinVar as [Benign]. Clinvar id is 905311.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANTXR2	NM_058172.6	c.*5602C>G		3_prime_UTR_variant	17/17	ENST00000403729.7
ANTXR2	NM_001286780.2	c.*5602C>G		3_prime_UTR_variant	17/17
ANTXR2	NM_001286781.2	c.*5602C>G		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR2	ENST00000403729.7	c.*5602C>G		3_prime_UTR_variant	17/17	1	NM_058172.6	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18699 AN: 151684 Hom.: 2432 Cov.: 30

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.0815 AC: 15 AN: 184 Hom.: 1 Cov.: 0 AF XY: 0.0797 AC XY: 11 AN XY: 138

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0592

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.123 AC: 18719 AN: 151804 Hom.: 2438 Cov.: 30 AF XY: 0.137 AC XY: 10148 AN XY: 74146

Gnomad4 AFR AF: 0.0559

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0809

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0412 Hom.: 35

Bravo AF: 0.129

Asia WGS AF: 0.455 AC: 1579 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyaline fibromatosis syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.3
Dann	Benign	0.41

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: rs4331719; hg19: chr4-80822981;