rs8135343

Variant names:

• chr22-37231805-G-A
• rs8135343
• NM_002872.5:c.288+127C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37231805-G-A
• chr22-37231805-G-C

Variant summary

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

The NM_002872.5(RAC2):​c.288+127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,117,006 control chromosomes in the GnomAD database, including 78,788 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 0.38 (11402 hom., cov: 30)
  • Exomes 𝑓: 0.37 (67386 hom.)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 14 publications found

Genes affected

RAC2 (HGNC:9802): (Rac family small GTPase 2) This gene encodes a member of the Ras superfamily of small guanosine triphosphate (GTP)-metabolizing proteins. The encoded protein localizes to the plasma membrane, where it regulates diverse processes, such as secretion, phagocytosis, and cell polarization. Activity of this protein is also involved in the generation of reactive oxygen species. Mutations in this gene are associated with neutrophil immunodeficiency syndrome. There is a pseudogene for this gene on chromosome 6. [provided by RefSeq, Jul 2013]

RAC2 Gene-Disease associations (from GenCC):

• immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen
• immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• neutrophil immunodeficiency syndrome

  Inheritance: Unknown, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC2	NM_002872.5	c.288+127C>T		intron_variant	Intron 4 of 6	ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4	c.288+127C>T		intron_variant	Intron 4 of 5		XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.288+127C>T		intron_variant	Intron 4 of 6	1	NM_002872.5	ENSP00000249071.6

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58290 AN: 151488 Hom.: 11374 Cov.: 30

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.370 AC: 357451 AN: 965400 Hom.: 67386 AF XY: 0.368 AC XY: 180160 AN XY: 489924

African (AFR) AF: 0.444 AC: 10235 AN: 23058

American (AMR) AF: 0.326 AC: 10994 AN: 33688

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 9384 AN: 21490

East Asian (EAS) AF: 0.305 AC: 10249 AN: 33606

South Asian (SAS) AF: 0.314 AC: 21768 AN: 69412

European-Finnish (FIN) AF: 0.322 AC: 12739 AN: 39510

Middle Eastern (MID) AF: 0.326 AC: 1094 AN: 3356

European-Non Finnish (NFE) AF: 0.379 AC: 264242 AN: 697848

Other (OTH) AF: 0.386 AC: 16746 AN: 43432

GnomAD4 genome AF: 0.385 AC: 58356 AN: 151606 Hom.: 11402 Cov.: 30 AF XY: 0.380 AC XY: 28171 AN XY: 74066

African (AFR) AF: 0.447 AC: 18482 AN: 41302

American (AMR) AF: 0.335 AC: 5108 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1496 AN: 3464

East Asian (EAS) AF: 0.322 AC: 1651 AN: 5128

South Asian (SAS) AF: 0.321 AC: 1539 AN: 4796

European-Finnish (FIN) AF: 0.328 AC: 3454 AN: 10532

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25453 AN: 67814

Other (OTH) AF: 0.385 AC: 810 AN: 2102

Alfa AF: 0.378 Hom.: 1772

Bravo AF: 0.389

Asia WGS AF: 0.323 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.4
DANN	Benign	0.80
PhyloP100		-1.4
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: rs8135343; hg19: chr22-37627845; COSMIC: COSV107218464; COSMIC: COSV107218464;