rs4984
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The ENST00000355733.7(ADD2):c.1797C>T(p.Ser599=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,613,672 control chromosomes in the GnomAD database, including 13,243 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 0.15 ( 1862 hom., cov: 32)
Exomes 𝑓: 0.12 ( 11381 hom. )
Consequence
ADD2
ENST00000355733.7 synonymous
ENST00000355733.7 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.60
Genes affected
ADD2 (HGNC:244): (adducin 2) Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma. The three subunits are encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. While adducins alpha and gamma are ubiquitously expressed, the expression of adducin beta is restricted to brain and hematopoietic tissues. Adducin, originally purified from human erythrocytes, was found to be a heterodimer of adducins alpha and beta. Polymorphisms resulting in amino acid substitutions in these two subunits have been associated with the regulation of blood pressure in an animal model of hypertension. Heterodimers consisting of alpha and gamma subunits have also been described. Structurally, each subunit is comprised of two distinct domains. The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive. The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP7
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Synonymous conserved (PhyloP=-1.6 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADD2 | NM_001617.4 | c.1742-265C>T | intron_variant | ENST00000264436.9 | |||
LOC105374794 | XR_940230.3 | n.17G>A | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADD2 | ENST00000264436.9 | c.1742-265C>T | intron_variant | 1 | NM_001617.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.149 AC: 22581AN: 151866Hom.: 1857 Cov.: 32
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GnomAD3 exomes AF: 0.120 AC: 30141AN: 251416Hom.: 2116 AF XY: 0.118 AC XY: 15974AN XY: 135884
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GnomAD4 exome AF: 0.121 AC: 176188AN: 1461690Hom.: 11381 Cov.: 31 AF XY: 0.120 AC XY: 87101AN XY: 727158
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GnomAD4 genome ? AF: 0.149 AC: 22618AN: 151982Hom.: 1862 Cov.: 32 AF XY: 0.146 AC XY: 10815AN XY: 74282
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Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at