chr2-70716718-A-C

Variant names:

• chr2-70716718-A-C
• rs7597774
• NM_001617.4:c.-153-3534T>G

Variant summary

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

The NM_001617.4(ADD2):​c.-153-3534T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,970 control chromosomes in the GnomAD database, including 20,454 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 0.49 (20454 hom., cov: 32)
• Consequence: ADD2 NM_001617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADD2	NM_001617.4	c.-153-3534T>G		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.-153-3534T>G		intron_variant	Intron 1 of 15	1	NM_001617.4	ENSP00000264436.3

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74585 AN: 151848 Hom.: 20424 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.491 AC: 74663 AN: 151970 Hom.: 20454 Cov.: 32 AF XY: 0.503 AC XY: 37369 AN XY: 74276

African (AFR) AF: 0.691 AC: 28636 AN: 41434

American (AMR) AF: 0.454 AC: 6934 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3468

East Asian (EAS) AF: 0.771 AC: 3953 AN: 5130

South Asian (SAS) AF: 0.539 AC: 2597 AN: 4818

European-Finnish (FIN) AF: 0.597 AC: 6313 AN: 10578

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23699 AN: 67942

Other (OTH) AF: 0.456 AC: 963 AN: 2112

Alfa AF: 0.396 Hom.: 4933

Bravo AF: 0.487

Asia WGS AF: 0.659 AC: 2291 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	8.1
DANN	Benign	0.66
PhyloP100		-0.60
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: rs7597774; hg19: chr2-70943850;