rs17698193

Variant names:

• chr2-70662366-A-G
• rs17698193
• NM_001617.4:c.*1059T>C

Variant summary

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

The ENST00000264436.9(ADD2):​c.*1059T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,122 control chromosomes in the GnomAD database, including 3,082 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 0.20 (3082 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: ADD2 ENST00000264436.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264436.9. 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.*1059T>C		3_prime_UTR	Exon 16 of 16	NP_001608.1
	ADD2	NM_001185054.2		c.*1059T>C		3_prime_UTR	Exon 16 of 16	NP_001171983.1
	ADD2	NM_017488.4		c.*1394T>C		3_prime_UTR	Exon 17 of 17	NP_059522.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD2	ENST00000264436.9	TSL:1 MANE Select	c.*1059T>C		3_prime_UTR	Exon 16 of 16	ENSP00000264436.3
	ADD2	ENST00000407644.6	TSL:1	c.*1059T>C		3_prime_UTR	Exon 16 of 16	ENSP00000384677.2
	ADD2	ENST00000403045.6	TSL:2	n.*181+878T>C		intron	N/A	ENSP00000384303.2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30040 AN: 151974 Hom.: 3081 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.167 AC: 5 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 4 AN XY: 24

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.125 AC: 1 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.143 AC: 2 AN: 14

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.198 AC: 30076 AN: 152092 Hom.: 3082 Cov.: 32 AF XY: 0.202 AC XY: 15049 AN XY: 74340

African (AFR) AF: 0.194 AC: 8063 AN: 41470

American (AMR) AF: 0.221 AC: 3386 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 758 AN: 3470

East Asian (EAS) AF: 0.149 AC: 770 AN: 5154

South Asian (SAS) AF: 0.257 AC: 1237 AN: 4820

European-Finnish (FIN) AF: 0.262 AC: 2771 AN: 10580

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12387 AN: 67994

Other (OTH) AF: 0.209 AC: 441 AN: 2106

Alfa AF: 0.186 Hom.: 10140

Bravo AF: 0.190

Asia WGS AF: 0.246 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.74
PhyloP100		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs17698193; hg19: chr2-70889498;