rs2272903

Variant names:

• chr6-50818858-G-A
• rs2272903
• XM_017011233.2:c.59G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-50818858-G-A
• chr6-50818858-G-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PP2 BP4_Moderate BA1

The XM_017011233.2(TFAP2B):​c.59G>A​(p.Ser20Asn) variant causes a missense change. The variant allele was found at a frequency of 0.126 in 1,600,400 control chromosomes in the GnomAD database, including 15,106 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2795 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12311 hom.)
• Consequence: TFAP2B XM_017011233.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.23
• Publications: 21 publications found

Genes affected

TFAP2B (HGNC:11743): (transcription factor AP-2 beta) This gene encodes a member of the AP-2 family of transcription factors. AP-2 proteins form homo- or hetero-dimers with other AP-2 family members and bind specific DNA sequences. They are thought to stimulate cell proliferation and suppress terminal differentiation of specific cell types during embryonic development. Specific AP-2 family members differ in their expression patterns and binding affinity for different promoters. This protein functions as both a transcriptional activator and repressor. Mutations in this gene result in autosomal dominant Char syndrome, suggesting that this gene functions in the differentiation of neural crest cell derivatives. [provided by RefSeq, Jul 2008]

TFAP2B Gene-Disease associations (from GenCC):

• Char syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• familial patent arterial duct

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000297125 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 8 curated pathogenic missense variants (we use a threshold of 10). The gene has 2 curated benign missense variants. Gene score misZ: 1.2875 (below the threshold of 3.09). Trascript score misZ: 1.5192 (below the threshold of 3.09). GenCC associations: The gene is linked to familial patent arterial duct, Char syndrome.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAP2B	NM_003221.4	c.-34G>A		upstream_gene_variant		ENST00000393655.4	NP_003212.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAP2B	ENST00000344788.7	c.-67G>A		5_prime_UTR_variant	Exon 1 of 4	3		ENSP00000342252.3
ENSG00000297125	ENST00000745639.1	n.343+44C>T		intron_variant	Intron 1 of 1
TFAP2B	ENST00000393655.4	c.-34G>A		upstream_gene_variant		1	NM_003221.4	ENSP00000377265.2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26273 AN: 151822 Hom.: 2792 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.169

GnomAD2 exomes AF: 0.149 AC: 37476 AN: 250704 AF XY: 0.149

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.228

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.122 AC: 176025 AN: 1448460 Hom.: 12311 Cov.: 28 AF XY: 0.123 AC XY: 88848 AN XY: 721588

African (AFR) AF: 0.299 AC: 9910 AN: 33184

American (AMR) AF: 0.121 AC: 5423 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4345 AN: 26054

East Asian (EAS) AF: 0.226 AC: 8936 AN: 39618

South Asian (SAS) AF: 0.189 AC: 16276 AN: 85952

European-Finnish (FIN) AF: 0.175 AC: 9327 AN: 53158

Middle Eastern (MID) AF: 0.163 AC: 937 AN: 5740

European-Non Finnish (NFE) AF: 0.102 AC: 112690 AN: 1100116

Other (OTH) AF: 0.136 AC: 8181 AN: 59948

GnomAD4 genome AF: 0.173 AC: 26288 AN: 151940 Hom.: 2795 Cov.: 32 AF XY: 0.179 AC XY: 13294 AN XY: 74268

African (AFR) AF: 0.290 AC: 12013 AN: 41382

American (AMR) AF: 0.146 AC: 2230 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1068 AN: 5154

South Asian (SAS) AF: 0.192 AC: 920 AN: 4802

European-Finnish (FIN) AF: 0.192 AC: 2028 AN: 10558

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6955 AN: 67978

Other (OTH) AF: 0.168 AC: 354 AN: 2108

Alfa AF: 0.132 Hom.: 3401

Bravo AF: 0.175

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Char syndrome Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.93
PhyloP100		6.2
PromoterAI		0.042	Neutral
Mutation Taster		=299/1	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: rs2272903; hg19: chr6-50786571; COSMIC: COSV53831805; COSMIC: COSV53831805;