rs7597992

Variant names:

• chr2-70716884-A-G
• rs7597992
• NM_001617.4:c.-153-3700T>C

Variant summary

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

The NM_001617.4(ADD2):​c.-153-3700T>C 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 152,008 control chromosomes in the GnomAD database, including 4,961 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 (4961 hom., cov: 32)
• Consequence: ADD2 NM_001617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADD2	NM_001617.4	c.-153-3700T>C		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.-153-3700T>C		intron_variant	Intron 1 of 15	1	NM_001617.4	ENSP00000264436.3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33026 AN: 151888 Hom.: 4951 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.218 AC: 33073 AN: 152008 Hom.: 4961 Cov.: 32 AF XY: 0.212 AC XY: 15783 AN XY: 74282

African (AFR) AF: 0.426 AC: 17653 AN: 41410

American (AMR) AF: 0.173 AC: 2640 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3468

East Asian (EAS) AF: 0.0450 AC: 233 AN: 5174

South Asian (SAS) AF: 0.116 AC: 558 AN: 4812

European-Finnish (FIN) AF: 0.115 AC: 1218 AN: 10580

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9464 AN: 67968

Other (OTH) AF: 0.215 AC: 452 AN: 2106

Alfa AF: 0.157 Hom.: 1571

Bravo AF: 0.231

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.54
PhyloP100		-0.044
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: rs7597992; hg19: chr2-70944016;