chr2-203407367-C-T

Position:

• chr2-203407367-C-T

Variant summary

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

The ENST00000261018.12(ABI2):​c.1193-3918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,020 control chromosomes in the GnomAD database, including 16,801 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 (16801 hom., cov: 33)
• Consequence: ABI2 ENST00000261018.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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]

RAPH1 (HGNC:14436): (Ras association (RalGDS/AF-6) and pleckstrin homology domains 1) This gene encodes a protein that belongs to the Mig10/Rap1-interacting adaptor molecule/Lamellipodin family of adapter proteins, which function in cell migration. Members of this family contain pleckstrin-homology domains, Ras-association domains, and proline-rich C-termini. The protein encoded by this gene regulates actin dynamics through interaction with Ena/Vasodilator proteins as well as direct binding to filamentous actin to regulate actin network assembly. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABI2	NM_001375670.1	c.1193-3918C>T		intron_variant		ENST00000261018.12	NP_001362599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABI2	ENST00000261018.12	c.1193-3918C>T		intron_variant		1	NM_001375670.1	ENSP00000261018

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67413 AN: 151904 Hom.: 16817 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.443 AC: 67394 AN: 152020 Hom.: 16801 Cov.: 33 AF XY: 0.443 AC XY: 32910 AN XY: 74290

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.485

Alfa AF: 0.539 Hom.: 40984

Bravo AF: 0.431

Asia WGS AF: 0.449 AC: 1562 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.59

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: rs1376877; hg19: chr2-204272090;