Variant rs1800847 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021784.5(FOXA2):c.309C>T(p.Ala103Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,528,470 control chromosomes in the GnomAD database, including 3,153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 733 hom., cov: 33)

Exomes 𝑓: 0.047 ( 2420 hom. )

Consequence

FOXA2
NM_021784.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.643

Variant links:

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]

FOXA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 20-22582933-G-A is Benign according to our data. Variant chr20-22582933-G-A is described in ClinVar as [Benign]. Clinvar id is 1569424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.643 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXA2	NM_021784.5 linkuse as main transcript	c.309C>T	p.Ala103Ala	synonymous_variant	2/2	ENST00000419308.7	NP_068556.2	Q9Y261-2B0ZTD4
FOXA2	NM_153675.3 linkuse as main transcript	c.291C>T	p.Ala97Ala	synonymous_variant	3/3		NP_710141.1	Q9Y261-1
FOXA2	XM_047440133.1 linkuse as main transcript	c.291C>T	p.Ala97Ala	synonymous_variant	3/3		XP_047296089.1
FOXA2	XM_047440134.1 linkuse as main transcript	c.201C>T	p.Ala67Ala	synonymous_variant	2/2		XP_047296090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXA2	ENST00000419308.7 linkuse as main transcript	c.309C>T	p.Ala103Ala	synonymous_variant	2/2	1	NM_021784.5	ENSP00000400341.3		Q9Y261-2
FOXA2	ENST00000377115.4 linkuse as main transcript	c.291C>T	p.Ala97Ala	synonymous_variant	3/3	1		ENSP00000366319.4		Q9Y261-1

Frequencies

GnomAD3 genomes

AF:

0.0799

AC:

12133

AN:

151914

Hom.:

727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.0453

Gnomad ASJ

AF:

0.0908

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.0870

Gnomad FIN

AF:

0.0233

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0401

Gnomad OTH

AF:

0.0786

GnomAD3 exomes

AF:

0.0712

AC:

9347

AN:

131320

Hom.:

517

AF XY:

0.0710

AC XY:

5194

AN XY:

73146

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.0342

Gnomad ASJ exome

AF:

0.0989

Gnomad EAS exome

AF:

0.180

Gnomad SAS exome

AF:

0.0971

Gnomad FIN exome

AF:

0.0258

Gnomad NFE exome

AF:

0.0468

Gnomad OTH exome

AF:

0.0658

GnomAD4 exome

AF:

0.0469

AC:

64568

AN:

1376450

Hom.:

2420

Cov.:

AF XY:

0.0481

AC XY:

32709

AN XY:

680274

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.0329

Gnomad4 ASJ exome

AF:

0.0913

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.0838

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.0355

Gnomad4 OTH exome

AF:

0.0639

GnomAD4 genome

AF:

0.0800

AC:

12161

AN:

152020

Hom.:

733

Cov.:

AF XY:

0.0792

AC XY:

5888

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.0452

Gnomad4 ASJ

AF:

0.0908

Gnomad4 EAS

AF:

0.157

Gnomad4 SAS

AF:

0.0869

Gnomad4 FIN

AF:

0.0233

Gnomad4 NFE

AF:

0.0401

Gnomad4 OTH

AF:

0.0802

Alfa

AF:

0.0361

Hom.:

Bravo

AF:

0.0849

Asia WGS

AF:

0.148

AC:

508

AN:

3452

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

FOXA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.1

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

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