17-39707009-G-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PVS1_SupportingBP6_ModerateBS1BS2
The NM_001005862.3(ERBB2):c.3G>T(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000164 in 1,594,508 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 2 hom. )
Consequence
ERBB2
NM_001005862.3 start_lost
NM_001005862.3 start_lost
Scores
4
10
4
Clinical Significance
Conservation
PhyloP100: 5.84
Genes affected
ERBB2 (HGNC:3430): (erb-b2 receptor tyrosine kinase 2) This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PVS1
Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 42 CDS bases. Genomic position: 39707048. Lost 0.011 part of the original CDS.
BP6
Variant 17-39707009-G-T is Benign according to our data. Variant chr17-39707009-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 134076.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000125 (19/152332) while in subpopulation SAS AF= 0.00393 (19/4830). AF 95% confidence interval is 0.00258. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000345 AC: 80AN: 231886Hom.: 2 AF XY: 0.000548 AC XY: 69AN XY: 126002
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GnomAD4 exome AF: 0.000168 AC: 243AN: 1442176Hom.: 2 Cov.: 30 AF XY: 0.000265 AC XY: 190AN XY: 716744
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74486
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 11, 2024 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;.;.;.;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;.;.;.;.;L;.
PrimateAI
Uncertain
T
PROVEAN
Benign
.;.;N;N;.;N;.
REVEL
Uncertain
Sift
Uncertain
.;.;D;T;.;D;.
Sift4G
Pathogenic
D;D;D;T;D;T;D
Polyphen
0.34, 0.31, 0.065
.;B;.;B;.;B;.
Vest4
MutPred
0.50
.;.;.;.;Loss of ubiquitination at K32 (P = 0.0598);Loss of ubiquitination at K32 (P = 0.0598);.;
MVP
MPC
0.50
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at