NM_001617.4:c.1871-3559T>A

Variant names:

• chr2-70667294-A-T
• rs10164951
• NM_001617.4:c.1871-3559T>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.1871-3559T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,734 control chromosomes in the GnomAD database, including 19,632 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 (19632 hom., cov: 30)
• Consequence: ADD2 NM_001617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 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.1871-3559T>A		intron	N/A	NP_001608.1
	ADD2	NM_001185054.2		c.1871-3559T>A		intron	N/A	NP_001171983.1
	ADD2	NM_017488.4		c.*25-3559T>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.1871-3559T>A		intron	N/A	ENSP00000264436.3
	ADD2	ENST00000407644.6	TSL:1	c.1871-3559T>A		intron	N/A	ENSP00000384677.2
	ADD2	ENST00000355733.7	TSL:1	c.*25-3559T>A		intron	N/A	ENSP00000347972.3

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73812 AN: 151616 Hom.: 19576 Cov.: 30

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.487 AC: 73940 AN: 151734 Hom.: 19632 Cov.: 30 AF XY: 0.482 AC XY: 35734 AN XY: 74116

African (AFR) AF: 0.719 AC: 29736 AN: 41374

American (AMR) AF: 0.437 AC: 6666 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1465 AN: 3462

East Asian (EAS) AF: 0.351 AC: 1807 AN: 5142

South Asian (SAS) AF: 0.439 AC: 2090 AN: 4764

European-Finnish (FIN) AF: 0.368 AC: 3872 AN: 10528

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

European-Non Finnish (NFE) AF: 0.394 AC: 26744 AN: 67920

Other (OTH) AF: 0.483 AC: 1014 AN: 2100

Alfa AF: 0.309 Hom.: 841

Bravo AF: 0.504

Asia WGS AF: 0.435 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		-0.38
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: rs10164951; hg19: chr2-70894426;