rs2277764

Positions:

• chr20-22585486-T-C
• chr20-22585486-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153675.3(FOXA2):​c.-213A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,244 control chromosomes in the GnomAD database, including 1,979 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1979 hom., cov: 33)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: FOXA2 NM_153675.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

Genes affected

FOXA2 (HGNC:5022): (forkhead box A2) This gene encodes a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific genes such as albumin and transthyretin, and they also interact with chromatin. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver. This gene has been linked to sporadic cases of maturity-onset diabetes of the young. Transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXA2	NM_153675.3	c.-213A>G		5_prime_UTR_variant	1/3		NP_710141.1
		n.22585486T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXA2	ENST00000377115.4	c.-213A>G		upstream_gene_variant		1		ENSP00000366319.4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17734 AN: 152110 Hom.: 1961 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0586

Gnomad ASJ AF: 0.0906

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0927

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0409

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.117 AC: 17788 AN: 152228 Hom.: 1979 Cov.: 33 AF XY: 0.115 AC XY: 8538 AN XY: 74440

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.0584

Gnomad4 ASJ AF: 0.0906

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.0922

Gnomad4 FIN AF: 0.0236

Gnomad4 NFE AF: 0.0409

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0283 Hom.: 30

Bravo AF: 0.127

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	17
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277764; hg19: chr20-22566124;