rs7225461

Positions:

• chr17-30932881-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018404.3(ADAP2):​c.397+913G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,966 control chromosomes in the GnomAD database, including 20,450 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 (20450 hom., cov: 32)
• Consequence: ADAP2 NM_018404.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430

Genes affected

ADAP2 (HGNC:16487): (ArfGAP with dual PH domains 2) The protein encoded by this gene binds beta-tubulin and increases the stability of microtubules. The encoded protein can also translocate to the cell membrane and bind phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4). In addition, this protein is a GTPase-activating protein for ADP ribosylation factor 6 and may be able to block the entry of some RNA viruses. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAP2	NM_018404.3	c.397+913G>A		intron_variant		ENST00000330889.8	NP_060874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAP2	ENST00000330889.8	c.397+913G>A		intron_variant		1	NM_018404.3	ENSP00000329468	A1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74139 AN: 151848 Hom.: 20395 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.489 AC: 74256 AN: 151966 Hom.: 20450 Cov.: 32 AF XY: 0.484 AC XY: 35943 AN XY: 74270

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.453

Alfa AF: 0.473 Hom.: 4275

Bravo AF: 0.502

Asia WGS AF: 0.372 AC: 1295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.18
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs7225461; hg19: chr17-29259899; COSMIC: COSV58296196;