2-70448449-C-T

Variant names:

• chr2-70448449-C-T
• rs473698
• NM_003236.4:c.*2410G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003236.4(TGFA):​c.*2410G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TGFA NM_003236.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 15 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4	c.*2410G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000295400.11	NP_003227.1
TGFA	NM_001308158.2	c.*2410G>A		3_prime_UTR_variant	Exon 6 of 6		NP_001295087.1
TGFA	NM_001308159.2	c.*2410G>A		3_prime_UTR_variant	Exon 6 of 6		NP_001295088.1
TGFA	NM_001099691.3	c.*2410G>A		3_prime_UTR_variant	Exon 6 of 6		NP_001093161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11	c.*2410G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_003236.4	ENSP00000295400.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.3
DANN	Benign	0.26
PhyloP100		0.028

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: rs473698; hg19: chr2-70675581;