Variant 20-22581844-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_021784.5(FOXA2):c.*6C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,607,094 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 8 hom. )

Consequence

FOXA2
NM_021784.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.81

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 20-22581844-G-A is Benign according to our data. Variant chr20-22581844-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1338703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 313 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
FOXA2	NM_021784.5 linkuse as main transcript	c.*6C>T	3_prime_UTR_variant	2/2	ENST00000419308.7	NP_068556.2
FOXA2	NM_153675.3 linkuse as main transcript	c.*6C>T	3_prime_UTR_variant	3/3		NP_710141.1
FOXA2	XM_047440133.1 linkuse as main transcript	c.*6C>T	3_prime_UTR_variant	3/3		XP_047296089.1
FOXA2	XM_047440134.1 linkuse as main transcript	c.*6C>T	3_prime_UTR_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.*6C>T		3_prime_UTR_variant	2/2	1	NM_021784.5	ENSP00000400341	P4	Q9Y261-2
FOXA2	ENST00000377115.4 linkuse as main transcript	c.*6C>T		3_prime_UTR_variant	3/3	1		ENSP00000366319	A1	Q9Y261-1

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

314

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00342

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00183

AC:

456

AN:

249286

Hom.:

AF XY:

0.00189

AC XY:

255

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.000402

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000787

Gnomad NFE exome

AF:

0.00339

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00328

AC:

4770

AN:

1454850

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

2249

AN XY:

722346

show subpopulations

Gnomad4 AFR exome

AF:

0.000510

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000930

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.00405

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00206

AC:

313

AN:

152244

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00341

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00274

Hom.:

Bravo

AF:

0.00214

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00332

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 11, 2021

- -

FOXA2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 18, 2019

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

FOXA2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.051

DANN

Benign

0.90

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