Variant rs903506 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004448.4(ERBB2):c.2086-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 1,612,328 control chromosomes in the GnomAD database, including 340,565 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 0.52 ( 23657 hom., cov: 32)

Exomes 𝑓: 0.65 ( 316908 hom. )

Consequence

ERBB2
NM_004448.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24

Variant links:

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]

ERBB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBB2	NM_004448.4 link	c.2086-29G>A		intron_variant		ENST00000269571.10	NP_004439.2	P04626-1X5DNK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBB2	ENST00000269571.10 link	c.2086-29G>A		intron_variant		1	NM_004448.4	ENSP00000269571.4		P04626-1

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

79326

AN:

152052

Hom.:

23648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.773

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.681

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.661

Gnomad OTH

AF:

0.540

GnomAD3 exomes

AF:

0.610

AC:

150465

AN:

246764

Hom.:

48102

AF XY:

0.626

AC XY:

83644

AN XY:

133676

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.570

Gnomad ASJ exome

AF:

0.690

Gnomad EAS exome

AF:

0.365

Gnomad SAS exome

AF:

0.690

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.672

Gnomad OTH exome

AF:

0.636

GnomAD4 exome

AF:

0.653

AC:

954101

AN:

1460158

Hom.:

316908

Cov.:

AF XY:

0.656

AC XY:

476579

AN XY:

726268

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.566

Gnomad4 ASJ exome

AF:

0.686

Gnomad4 EAS exome

AF:

0.441

Gnomad4 SAS exome

AF:

0.694

Gnomad4 FIN exome

AF:

0.677

Gnomad4 NFE exome

AF:

0.674

Gnomad4 OTH exome

AF:

0.627

GnomAD4 genome

AF:

0.521

AC:

79349

AN:

152170

Hom.:

23657

Cov.:

AF XY:

0.521

AC XY:

38779

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.530

Gnomad4 ASJ

AF:

0.677

Gnomad4 EAS

AF:

0.394

Gnomad4 SAS

AF:

0.660

Gnomad4 FIN

AF:

0.681

Gnomad4 NFE

AF:

0.661

Gnomad4 OTH

AF:

0.541

Alfa

AF:

0.608

Hom.:

5474

Bravo

AF:

0.494

Asia WGS

AF:

0.559

AC:

1943

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.34

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over