chr10-24584810-C-T

Position:

• chr10-24584810-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020824.4(ARHGAP21):​c.5479G>A​(p.Glu1827Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP21 NM_020824.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.66

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18648264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP21	NM_020824.4	c.5479G>A	p.Glu1827Lys	missense_variant	26/26	ENST00000396432.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP21	ENST00000396432.7	c.5479G>A	p.Glu1827Lys	missense_variant	26/26	1	NM_020824.4	A2

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

Oct 17, 2023

The c.5479G>A (p.E1827K) alteration is located in exon 26 (coding exon 25) of the ARHGAP21 gene. This alteration results from a G to A substitution at nucleotide position 5479, causing the glutamic acid (E) at amino acid position 1827 to be replaced by a lysine (K). 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	0.090
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Uncertain	0.98
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.77	N;.;.
REVEL	Benign	0.046
Sift	Uncertain	0.0060	D;.;.
Sift4G	Uncertain	0.044	D;T;T
Vest4		0.32
MVP		0.082
MPC		0.51
ClinPred		0.50	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-24873739;