chr2-70693531-C-T

Position:

• chr2-70693531-C-T

Variant summary

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

The ENST00000264436.9(ADD2):​c.556-979G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,992 control chromosomes in the GnomAD database, including 7,131 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 0.30 (7131 hom., cov: 32)
• Consequence: ADD2 ENST00000264436.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.711

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADD2	NM_001617.4	c.556-979G>A		intron_variant		ENST00000264436.9	NP_001608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADD2	ENST00000264436.9	c.556-979G>A		intron_variant		1	NM_001617.4	ENSP00000264436	P2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45512 AN: 151874 Hom.: 7122 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.281

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.300 AC: 45584 AN: 151992 Hom.: 7131 Cov.: 32 AF XY: 0.300 AC XY: 22313 AN XY: 74294

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.284

Alfa AF: 0.153 Hom.: 271

Bravo AF: 0.306

Asia WGS AF: 0.378 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.41

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: rs3755375; hg19: chr2-70920663;