2-70694407-C-T

Variant names:

• chr2-70694407-C-T
• rs4852700
• NM_001617.4:c.555+1314G>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.555+1314G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,012 control chromosomes in the GnomAD database, including 43,564 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 0.75 (43564 hom., cov: 31)
• Consequence: ADD2 NM_001617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 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.555+1314G>A		intron	N/A	NP_001608.1
	ADD2	NM_001185054.2		c.555+1314G>A		intron	N/A	NP_001171983.1
	ADD2	NM_017488.4		c.555+1314G>A		intron	N/A	NP_059522.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD2	ENST00000264436.9	TSL:1 MANE Select	c.555+1314G>A		intron	N/A	ENSP00000264436.3
	ADD2	ENST00000407644.6	TSL:1	c.555+1314G>A		intron	N/A	ENSP00000384677.2
	ADD2	ENST00000355733.7	TSL:1	c.555+1314G>A		intron	N/A	ENSP00000347972.3

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114418 AN: 151894 Hom.: 43508 Cov.: 31

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.754 AC: 114546 AN: 152012 Hom.: 43564 Cov.: 31 AF XY: 0.744 AC XY: 55266 AN XY: 74286

African (AFR) AF: 0.820 AC: 34014 AN: 41468

American (AMR) AF: 0.737 AC: 11253 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2818 AN: 3470

East Asian (EAS) AF: 0.583 AC: 3001 AN: 5146

South Asian (SAS) AF: 0.669 AC: 3216 AN: 4808

European-Finnish (FIN) AF: 0.592 AC: 6241 AN: 10542

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51582 AN: 67984

Other (OTH) AF: 0.760 AC: 1608 AN: 2116

Alfa AF: 0.760 Hom.: 70824

Bravo AF: 0.766

Asia WGS AF: 0.677 AC: 2355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.46
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: rs4852700; hg19: chr2-70921539;