rs758062

Variant names:

• chr2-70668930-C-T
• rs758062
• NM_001617.4:c.1870+3948G>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.1870+3948G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,076 control chromosomes in the GnomAD database, including 19,308 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 0.48 (19308 hom., cov: 32)
• Consequence: ADD2 NM_001617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001617.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD2	NM_001617.4	MANE Select	c.1870+3948G>A		intron	N/A	NP_001608.1
	ADD2	NM_001185054.2		c.1870+3948G>A		intron	N/A	NP_001171983.1
	ADD2	NM_017488.4		c.*24+3948G>A		intron	N/A	NP_059522.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD2	ENST00000264436.9	TSL:1 MANE Select	c.1870+3948G>A		intron	N/A	ENSP00000264436.3
	ADD2	ENST00000407644.6	TSL:1	c.1870+3948G>A		intron	N/A	ENSP00000384677.2
	ADD2	ENST00000355733.7	TSL:1	c.*24+3948G>A		intron	N/A	ENSP00000347972.3

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73094 AN: 151958 Hom.: 19252 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.481 AC: 73224 AN: 152076 Hom.: 19308 Cov.: 32 AF XY: 0.477 AC XY: 35463 AN XY: 74338

African (AFR) AF: 0.717 AC: 29728 AN: 41490

American (AMR) AF: 0.429 AC: 6544 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1445 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1832 AN: 5186

South Asian (SAS) AF: 0.441 AC: 2121 AN: 4814

European-Finnish (FIN) AF: 0.364 AC: 3850 AN: 10568

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26156 AN: 67980

Other (OTH) AF: 0.475 AC: 1001 AN: 2106

Alfa AF: 0.422 Hom.: 21436

Bravo AF: 0.497

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.82
PhyloP100		-0.0050
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: rs758062; hg19: chr2-70896062;