rs1212275

Variant names:

• chr20-22582036-T-C
• rs1212275
• NM_021784.5:c.1206A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-22582036-T-C
• chr20-22582036-T-A

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.1206A>G​(p.Gln402Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 1,613,626 control chromosomes in the GnomAD database, including 621,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (62772 hom., cov: 32)
  • Exomes 𝑓: 0.87 (558700 hom.)
• Consequence: FOXA2 NM_021784.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0760
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• combined pituitary hormone deficiencies, genetic form

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-22582036-T-C is Benign according to our data. Variant chr20-22582036-T-C is described in ClinVar as Benign. ClinVar VariationId is 1300560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.076 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021784.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXA2	NM_021784.5	MANE Select	c.1206A>G	p.Gln402Gln	synonymous	Exon 2 of 2	NP_068556.2	B0ZTD4
	FOXA2	NM_153675.3		c.1188A>G	p.Gln396Gln	synonymous	Exon 3 of 3	NP_710141.1	Q9Y261-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXA2	ENST00000419308.7	TSL:1 MANE Select	c.1206A>G	p.Gln402Gln	synonymous	Exon 2 of 2	ENSP00000400341.3	Q9Y261-2
	FOXA2	ENST00000377115.4	TSL:1	c.1188A>G	p.Gln396Gln	synonymous	Exon 3 of 3	ENSP00000366319.4	Q9Y261-1
	FOXA2	ENST00000938926.1		c.681A>G	p.Gln227Gln	synonymous	Exon 2 of 2	ENSP00000608985.1

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137923 AN: 152074 Hom.: 62712 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.894

GnomAD2 exomes AF: 0.901 AC: 225247 AN: 249896 AF XY: 0.900

Gnomad AFR exome AF: 0.976

Gnomad AMR exome AF: 0.937

Gnomad ASJ exome AF: 0.887

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.872

Gnomad NFE exome AF: 0.857

Gnomad OTH exome AF: 0.878

GnomAD4 exome AF: 0.873 AC: 1276442 AN: 1461434 Hom.: 558700 Cov.: 91 AF XY: 0.876 AC XY: 636719 AN XY: 727024

African (AFR) AF: 0.977 AC: 32709 AN: 33472

American (AMR) AF: 0.936 AC: 41835 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 23203 AN: 26128

East Asian (EAS) AF: 1.00 AC: 39665 AN: 39682

South Asian (SAS) AF: 0.957 AC: 82486 AN: 86194

European-Finnish (FIN) AF: 0.872 AC: 46559 AN: 53396

Middle Eastern (MID) AF: 0.876 AC: 5055 AN: 5768

European-Non Finnish (NFE) AF: 0.856 AC: 951559 AN: 1111724

Other (OTH) AF: 0.884 AC: 53371 AN: 60378

GnomAD4 genome AF: 0.907 AC: 138042 AN: 152192 Hom.: 62772 Cov.: 32 AF XY: 0.910 AC XY: 67654 AN XY: 74384

African (AFR) AF: 0.975 AC: 40540 AN: 41566

American (AMR) AF: 0.909 AC: 13907 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3078 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5146 AN: 5146

South Asian (SAS) AF: 0.966 AC: 4665 AN: 4828

European-Finnish (FIN) AF: 0.879 AC: 9302 AN: 10578

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58438 AN: 67978

Other (OTH) AF: 0.895 AC: 1893 AN: 2114

Alfa AF: 0.879 Hom.: 114749

Bravo AF: 0.912

Asia WGS AF: 0.980 AC: 3408 AN: 3478

EpiCase AF: 0.859

EpiControl AF: 0.858

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.47
PhyloP100		-0.076
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

Other links and lift over

dbSNP: rs1212275; hg19: chr20-22562674; COSMIC: COSV108235352; COSMIC: COSV108235352;