chr2-203384676-A-G

Variant names:

• chr2-203384676-A-G
• rs11675251
• NM_001375670.1:c.480+2470A>G

Variant summary

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

The NM_001375670.1(ABI2):​c.480+2470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,740 control chromosomes in the GnomAD database, including 16,814 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 0.44 (16814 hom., cov: 30)
• Consequence: ABI2 NM_001375670.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• Publications: 19 publications found

Genes affected

ABI2 (HGNC:24011): (abl interactor 2) Enables several functions, including SH3 domain binding activity; identical protein binding activity; and ubiquitin protein ligase binding activity. Contributes to small GTPase binding activity. Involved in Rac protein signal transduction; positive regulation of cellular component organization; and zonula adherens assembly. Acts upstream of or within peptidyl-tyrosine phosphorylation. Located in several cellular components, including filopodium tip; lamellipodium; and nucleoplasm. Part of SCAR complex. Is active in adherens junction. Colocalizes with actin filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375670.1. 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
	ABI2	NM_001375670.1	MANE Select	c.480+2470A>G		intron	N/A	NP_001362599.1
	ABI2	NM_001375671.1		c.480+2470A>G		intron	N/A	NP_001362600.1
	ABI2	NM_001375672.1		c.480+2470A>G		intron	N/A	NP_001362601.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABI2	ENST00000261018.12	TSL:1 MANE Select	c.480+2470A>G		intron	N/A	ENSP00000261018.9
	ABI2	ENST00000295851.10	TSL:1	c.480+2470A>G		intron	N/A	ENSP00000295851.4
	ABI2	ENST00000417864.5	TSL:1	c.480+2470A>G		intron	N/A	ENSP00000414703.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67409 AN: 151622 Hom.: 16830 Cov.: 30

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.444 AC: 67390 AN: 151740 Hom.: 16814 Cov.: 30 AF XY: 0.444 AC XY: 32901 AN XY: 74132

African (AFR) AF: 0.218 AC: 9028 AN: 41382

American (AMR) AF: 0.480 AC: 7317 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2278 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1547 AN: 5162

South Asian (SAS) AF: 0.610 AC: 2932 AN: 4806

European-Finnish (FIN) AF: 0.450 AC: 4720 AN: 10498

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.556 AC: 37753 AN: 67880

Other (OTH) AF: 0.486 AC: 1022 AN: 2104

Alfa AF: 0.522 Hom.: 64855

Bravo AF: 0.432

Asia WGS AF: 0.450 AC: 1567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.56
PhyloP100		2.0
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: rs11675251; hg19: chr2-204249399;