rs2270042

chr2-70687913-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001617.4(ADD2):c.948+111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 729,222 control chromosomes in the GnomAD database, including 26,537 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 0.29 (6764 hom., cov: 33)
  • Exomes 𝑓: 0.26 (19773 hom.)
• Consequence: ADD2 NM_001617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADD2	NM_001617.4	c.948+111A>G		intron_variant		ENST00000264436.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADD2	ENST00000264436.9	c.948+111A>G		intron_variant		1	NM_001617.4	P2
	ENST00000457851.1	n.217+555T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44034 AN: 152030 Hom.: 6755 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.256 AC: 147819 AN: 577074 Hom.: 19773 AF XY: 0.259 AC XY: 79141 AN XY: 305410

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.290 AC: 44107 AN: 152148 Hom.: 6764 Cov.: 33 AF XY: 0.291 AC XY: 21623 AN XY: 74384

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.274

Alfa AF: 0.257 Hom.: 1032

Bravo AF: 0.296

Asia WGS AF: 0.377 AC: 1308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.0040
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2270042; hg19: chr2-70915045;