Variant rs1203910 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.855A>G(p.Gly285Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 1,541,352 control chromosomes in the GnomAD database, including 10,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 4604 hom., cov: 33)

Exomes 𝑓: 0.058 ( 5790 hom. )

Consequence

FOXA2
NM_021784.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.201

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=-0.92).

BP6

Variant 20-22582387-T-C is Benign according to our data. Variant chr20-22582387-T-C is described in ClinVar as [Benign]. Clinvar id is 1601694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.201 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 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.855A>G	p.Gly285Gly	synonymous_variant	2/2	ENST00000419308.7	NP_068556.2	Q9Y261-2B0ZTD4
FOXA2	NM_153675.3 linkuse as main transcript	c.837A>G	p.Gly279Gly	synonymous_variant	3/3		NP_710141.1	Q9Y261-1
FOXA2	XM_047440133.1 linkuse as main transcript	c.837A>G	p.Gly279Gly	synonymous_variant	3/3		XP_047296089.1
FOXA2	XM_047440134.1 linkuse as main transcript	c.747A>G	p.Gly249Gly	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.855A>G	p.Gly285Gly	synonymous_variant	2/2	1	NM_021784.5	ENSP00000400341.3		Q9Y261-2
FOXA2	ENST00000377115.4 linkuse as main transcript	c.837A>G	p.Gly279Gly	synonymous_variant	3/3	1		ENSP00000366319.4		Q9Y261-1

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25115

AN:

152050

Hom.:

4567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.0756

Gnomad ASJ

AF:

0.0963

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.0433

Gnomad OTH

AF:

0.147

GnomAD3 exomes

AF:

0.0869

AC:

13607

AN:

156562

Hom.:

1406

AF XY:

0.0828

AC XY:

7126

AN XY:

86062

show subpopulations

Gnomad AFR exome

AF:

0.465

Gnomad AMR exome

AF:

0.0442

Gnomad ASJ exome

AF:

0.0988

Gnomad EAS exome

AF:

0.183

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0250

Gnomad NFE exome

AF:

0.0421

Gnomad OTH exome

AF:

0.0710

GnomAD4 exome

AF:

0.0577

AC:

80181

AN:

1389188

Hom.:

5790

Cov.:

AF XY:

0.0584

AC XY:

40049

AN XY:

685574

show subpopulations

Gnomad4 AFR exome

AF:

0.463

Gnomad4 AMR exome

AF:

0.0480

Gnomad4 ASJ exome

AF:

0.0948

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.0267

Gnomad4 NFE exome

AF:

0.0374

Gnomad4 OTH exome

AF:

0.0884

GnomAD4 genome

AF:

0.166

AC:

25199

AN:

152164

Hom.:

4604

Cov.:

AF XY:

0.163

AC XY:

12099

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.447

Gnomad4 AMR

AF:

0.0754

Gnomad4 ASJ

AF:

0.0963

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.0434

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.0952

Hom.:

356

Bravo

AF:

0.183

Asia WGS

AF:

0.203

AC:

704

AN:

3478

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

-0.92

CADD

Benign

2.7

DANN

Benign

0.52

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