2-70523399-T-C

Variant names:

• chr2-70523399-T-C
• rs426081
• NM_003236.4:c.41-8487A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003236.4(TGFA):​c.41-8487A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,064 control chromosomes in the GnomAD database, including 9,015 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (9015 hom., cov: 32)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 5 publications found

Genes affected

TGFA (HGNC:11765): (transforming growth factor alpha) This gene encodes a growth factor that is a ligand for the epidermal growth factor receptor, which activates a signaling pathway for cell proliferation, differentiation and development. This protein may act as either a transmembrane-bound ligand or a soluble ligand. This gene has been associated with many types of cancers, and it may also be involved in some cases of cleft lip/palate. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

TGFA Gene-Disease associations (from GenCC):

• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.41-8487A>G		intron_variant	Intron 1 of 5	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.59-8487A>G		intron_variant	Intron 1 of 5		NP_001295087.1
TGFA	NM_001308159.2	c.59-8487A>G		intron_variant	Intron 1 of 5		NP_001295088.1
TGFA	NM_001099691.3	c.41-8487A>G		intron_variant	Intron 1 of 5		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.41-8487A>G		intron_variant	Intron 1 of 5	1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45057 AN: 151946 Hom.: 8985 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45137 AN: 152064 Hom.: 9015 Cov.: 32 AF XY: 0.294 AC XY: 21890 AN XY: 74372

African (AFR) AF: 0.566 AC: 23460 AN: 41424

American (AMR) AF: 0.261 AC: 3994 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3470

East Asian (EAS) AF: 0.106 AC: 547 AN: 5184

South Asian (SAS) AF: 0.309 AC: 1489 AN: 4824

European-Finnish (FIN) AF: 0.163 AC: 1730 AN: 10594

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12460 AN: 67978

Other (OTH) AF: 0.273 AC: 576 AN: 2108

Alfa AF: 0.215 Hom.: 17337

Bravo AF: 0.313

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.020
DANN	Benign	0.50
PhyloP100		-2.9
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: rs426081; hg19: chr2-70750531;