chr2-70493874-A-G

Variant names:

• chr2-70493874-A-G
• rs3821262
• NM_003236.4:c.94+20985T>C

Variant summary

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

The NM_003236.4(TGFA):​c.94+20985T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,014 control chromosomes in the GnomAD database, including 17,607 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 0.48 (17607 hom., cov: 32)
• Consequence: TGFA NM_003236.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003236.4. 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
	TGFA	NM_003236.4	MANE Select	c.94+20985T>C		intron	N/A	NP_003227.1
	TGFA	NM_001308158.2		c.112+20985T>C		intron	N/A	NP_001295087.1
	TGFA	NM_001308159.2		c.112+20985T>C		intron	N/A	NP_001295088.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFA	ENST00000295400.11	TSL:1 MANE Select	c.94+20985T>C		intron	N/A	ENSP00000295400.6
	TGFA	ENST00000444975.5	TSL:1	c.112+20985T>C		intron	N/A	ENSP00000404131.1
	TGFA	ENST00000450929.5	TSL:1	c.112+20985T>C		intron	N/A	ENSP00000414127.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72602 AN: 151896 Hom.: 17582 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.478 AC: 72660 AN: 152014 Hom.: 17607 Cov.: 32 AF XY: 0.480 AC XY: 35699 AN XY: 74304

African (AFR) AF: 0.450 AC: 18668 AN: 41496

American (AMR) AF: 0.521 AC: 7956 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3468

East Asian (EAS) AF: 0.580 AC: 2988 AN: 5150

South Asian (SAS) AF: 0.423 AC: 2036 AN: 4816

European-Finnish (FIN) AF: 0.556 AC: 5865 AN: 10558

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.477 AC: 32408 AN: 67932

Other (OTH) AF: 0.467 AC: 987 AN: 2114

Alfa AF: 0.474 Hom.: 9673

Bravo AF: 0.482

Asia WGS AF: 0.503 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.36
PhyloP100		-0.043
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: rs3821262; hg19: chr2-70721006;