rs1203910

Variant names:

• chr20-22582387-T-C
• rs1203910
• NM_021784.5:c.855A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-22582387-T-C
• chr20-22582387-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.201

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FOXA2	NM_021784.5	c.855A>G	p.Gly285Gly	synonymous_variant	Exon 2 of 2	ENST00000419308.7	NP_068556.2
FOXA2	NM_153675.3	c.837A>G	p.Gly279Gly	synonymous_variant	Exon 3 of 3		NP_710141.1
FOXA2	XM_047440133.1	c.837A>G	p.Gly279Gly	synonymous_variant	Exon 3 of 3		XP_047296089.1
FOXA2	XM_047440134.1	c.747A>G	p.Gly249Gly	synonymous_variant	Exon 2 of 2		XP_047296090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXA2	ENST00000419308.7	c.855A>G	p.Gly285Gly	synonymous_variant	Exon 2 of 2	1	NM_021784.5	ENSP00000400341.3
FOXA2	ENST00000377115.4	c.837A>G	p.Gly279Gly	synonymous_variant	Exon 3 of 3	1		ENSP00000366319.4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25115 AN: 152050 Hom.: 4567 Cov.: 33

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

GnomAD2 exomes AF: 0.0869 AC: 13607 AN: 156562 AF XY: 0.0828

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 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.: 35 AF XY: 0.0584 AC XY: 40049 AN XY: 685574

Gnomad4 AFR exome AF: 0.463 AC: 14179 AN: 30652

Gnomad4 AMR exome AF: 0.0480 AC: 1621 AN: 33782

Gnomad4 ASJ exome AF: 0.0948 AC: 2137 AN: 22542

Gnomad4 EAS exome AF: 0.197 AC: 7506 AN: 38098

Gnomad4 SAS exome AF: 0.100 AC: 7547 AN: 75146

Gnomad4 FIN exome AF: 0.0267 AC: 1202 AN: 44960

Gnomad4 NFE exome AF: 0.0374 AC: 40515 AN: 1082876

Gnomad4 Remaining exome AF: 0.0884 AC: 5051 AN: 57128

GnomAD4 genome AF: 0.166 AC: 25199 AN: 152164 Hom.: 4604 Cov.: 33 AF XY: 0.163 AC XY: 12099 AN XY: 74358

Gnomad4 AFR AF: 0.447 AC: 0.446921 AN: 0.446921

Gnomad4 AMR AF: 0.0754 AC: 0.075415 AN: 0.075415

Gnomad4 ASJ AF: 0.0963 AC: 0.0962536 AN: 0.0962536

Gnomad4 EAS AF: 0.194 AC: 0.193643 AN: 0.193643

Gnomad4 SAS AF: 0.107 AC: 0.107084 AN: 0.107084

Gnomad4 FIN AF: 0.0235 AC: 0.0234684 AN: 0.0234684

Gnomad4 NFE AF: 0.0434 AC: 0.0433798 AN: 0.0433798

Gnomad4 OTH AF: 0.148 AC: 0.148061 AN: 0.148061

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FOXA2-related disorder Benign:1

Sep 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
Mutation Taster		=100/0	polymorphism (auto)

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: rs1203910; hg19: chr20-22563025; COSMIC: COSV65795735; COSMIC: COSV65795735;