10-24584602-G-C

Position:

• chr10-24584602-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020824.4(ARHGAP21):​c.5687C>G​(p.Thr1896Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP21 NM_020824.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.229

Genes affected

ARHGAP21 (HGNC:23725): (Rho GTPase activating protein 21) ARHGAP21 functions preferentially as a GTPase-activating protein (GAP) for CDC42 (MIM 116952) and regulates the ARP2/3 complex (MIM 604221) and F-actin dynamics at the Golgi through control of CDC42 activity (Dubois et al., 2005 [PubMed 15793564]).[supplied by OMIM, Mar 2008]

ARHGAP21 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05215937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP21	NM_020824.4	c.5687C>G	p.Thr1896Arg	missense_variant	26/26	ENST00000396432.7	NP_065875.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP21	ENST00000396432.7	c.5687C>G	p.Thr1896Arg	missense_variant	26/26	1	NM_020824.4	ENSP00000379709.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2024

The c.5687C>G (p.T1896R) alteration is located in exon 26 (coding exon 25) of the ARHGAP21 gene. This alteration results from a C to G substitution at nucleotide position 5687, causing the threonine (T) at amino acid position 1896 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.8
DANN	Benign	0.79
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.040	N;.;.
REVEL	Benign	0.077
Sift	Benign	0.18	T;.;.
Sift4G	Benign	0.52	T;T;T
Vest4		0.069
MVP		0.043
MPC		0.49
ClinPred		0.053	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1592896471; hg19: chr10-24873531;