rs13416248

Variant names:

• chr2-70754321-C-T
• rs13416248
• NM_001617.4:c.-154+13565G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001617.4(ADD2):​c.-154+13565G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,984 control chromosomes in the GnomAD database, including 4,190 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 0.22 (4190 hom., cov: 31)
• Consequence: ADD2 NM_001617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADD2	NM_001617.4	c.-154+13565G>A		intron_variant	Intron 1 of 15	ENST00000264436.9	NP_001608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADD2	ENST00000264436.9	c.-154+13565G>A		intron_variant	Intron 1 of 15	1	NM_001617.4	ENSP00000264436.3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33153 AN: 151866 Hom.: 4197 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.218 AC: 33160 AN: 151984 Hom.: 4190 Cov.: 31 AF XY: 0.229 AC XY: 17035 AN XY: 74274

African (AFR) AF: 0.146 AC: 6064 AN: 41434

American (AMR) AF: 0.300 AC: 4585 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2448 AN: 5150

South Asian (SAS) AF: 0.331 AC: 1594 AN: 4810

European-Finnish (FIN) AF: 0.343 AC: 3622 AN: 10554

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13727 AN: 67978

Other (OTH) AF: 0.204 AC: 431 AN: 2112

Alfa AF: 0.210 Hom.: 8717

Bravo AF: 0.212

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13416248; hg19: chr2-70981453;