2-70707609-G-C

Variant names:

• chr2-70707609-G-C
• rs2110981
• NM_001617.4:c.-34-1167C>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.-34-1167C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,202 control chromosomes in the GnomAD database, including 9,637 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 0.34 (9637 hom., cov: 34)
• Consequence: ADD2 NM_001617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD2	NM_001617.4	MANE Select	c.-34-1167C>G		intron	N/A	NP_001608.1	P35612-1
	ADD2	NM_001185054.2		c.-34-1167C>G		intron	N/A	NP_001171983.1	P35612-1
	ADD2	NM_017488.4		c.-34-1167C>G		intron	N/A	NP_059522.1	P35612-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD2	ENST00000264436.9	TSL:1 MANE Select	c.-34-1167C>G		intron	N/A	ENSP00000264436.3	P35612-1
	ADD2	ENST00000407644.6	TSL:1	c.-34-1167C>G		intron	N/A	ENSP00000384677.2	P35612-1
	ADD2	ENST00000355733.7	TSL:1	c.-34-1167C>G		intron	N/A	ENSP00000347972.3	P35612-3

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51634 AN: 152084 Hom.: 9614 Cov.: 34

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.340 AC: 51721 AN: 152202 Hom.: 9637 Cov.: 34 AF XY: 0.342 AC XY: 25422 AN XY: 74420

African (AFR) AF: 0.504 AC: 20937 AN: 41518

American (AMR) AF: 0.316 AC: 4833 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2322 AN: 5178

South Asian (SAS) AF: 0.354 AC: 1709 AN: 4826

European-Finnish (FIN) AF: 0.279 AC: 2954 AN: 10582

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17099 AN: 68018

Other (OTH) AF: 0.317 AC: 669 AN: 2112

Alfa AF: 0.168 Hom.: 303

Bravo AF: 0.350

Asia WGS AF: 0.413 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.45
PhyloP100		-0.77
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: rs2110981; hg19: chr2-70934741;