2-70514890-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003236.4(TGFA):​c.63G>A​(p.Gln21Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,614,062 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 16 hom., cov: 32)
Exomes 𝑓: 0.00094 ( 26 hom. )

Consequence

TGFA
NM_003236.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.207

Publications

4 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 2-70514890-C-T is Benign according to our data. Variant chr2-70514890-C-T is described in ClinVar as [Benign]. Clinvar id is 787233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.207 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00875 (1333/152340) while in subpopulation AFR AF = 0.0302 (1256/41572). AF 95% confidence interval is 0.0288. There are 16 homozygotes in GnomAd4. There are 621 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 1333 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TGFANM_003236.4 linkc.63G>A p.Gln21Gln synonymous_variant Exon 2 of 6 ENST00000295400.11 NP_003227.1 P01135-1
TGFANM_001308158.2 linkc.81G>A p.Gln27Gln synonymous_variant Exon 2 of 6 NP_001295087.1 P01135F8VNR3
TGFANM_001308159.2 linkc.81G>A p.Gln27Gln synonymous_variant Exon 2 of 6 NP_001295088.1 P01135E7EPT6
TGFANM_001099691.3 linkc.63G>A p.Gln21Gln synonymous_variant Exon 2 of 6 NP_001093161.1 P01135-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TGFAENST00000295400.11 linkc.63G>A p.Gln21Gln synonymous_variant Exon 2 of 6 1 NM_003236.4 ENSP00000295400.6 P01135-1

Frequencies

GnomAD3 genomes
AF:
0.00873
AC:
1329
AN:
152222
Hom.:
16
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0302
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00399
Gnomad ASJ
AF:
0.00230
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00191
GnomAD2 exomes
AF:
0.00248
AC:
622
AN:
250656
AF XY:
0.00197
show subpopulations
Gnomad AFR exome
AF:
0.0324
Gnomad AMR exome
AF:
0.00177
Gnomad ASJ exome
AF:
0.00249
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000618
Gnomad OTH exome
AF:
0.000817
GnomAD4 exome
AF:
0.000938
AC:
1371
AN:
1461722
Hom.:
26
Cov.:
31
AF XY:
0.000803
AC XY:
584
AN XY:
727144
show subpopulations
African (AFR)
AF:
0.0309
AC:
1036
AN:
33476
American (AMR)
AF:
0.00192
AC:
86
AN:
44706
Ashkenazi Jewish (ASJ)
AF:
0.00260
AC:
68
AN:
26128
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86196
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53384
Middle Eastern (MID)
AF:
0.00139
AC:
8
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000360
AC:
40
AN:
1111978
Other (OTH)
AF:
0.00219
AC:
132
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.473
Heterozygous variant carriers
0
65
129
194
258
323
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
36
72
108
144
180
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00875
AC:
1333
AN:
152340
Hom.:
16
Cov.:
32
AF XY:
0.00834
AC XY:
621
AN XY:
74490
show subpopulations
African (AFR)
AF:
0.0302
AC:
1256
AN:
41572
American (AMR)
AF:
0.00398
AC:
61
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
0.00230
AC:
8
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5176
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68038
Other (OTH)
AF:
0.00189
AC:
4
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
69
138
206
275
344
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00421
Hom.:
13
Bravo
AF:
0.00991
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Nov 20, 2018
Labcorp Genetics (formerly Invitae), Labcorp
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
-0.53
CADD
Benign
2.4
DANN
Benign
0.86
PhyloP100
-0.21
Mutation Taster
=99/1
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs10183171; hg19: chr2-70742022; API