rs147193304

chr12-45850702-A-Gchr12-45850702-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2 BP4_Moderate BS1_Supporting BS2

The NM_152641.4(ARID2):c.2579A>G(p.Asn860Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N860D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ARID2 NM_152641.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.78

Genes affected

ARID2 (HGNC:18037): (AT-rich interaction domain 2) This gene encodes a member of the AT-rich interactive domain (ARID)-containing family of DNA-binding proteins. Members of the ARID family have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation and chromatin structure modification. This protein functions as a subunit of the polybromo- and BRG1-associated factor or PBAF (SWI/SNF-B) chromatin remodeling complex which facilitates ligand-dependent transcriptional activation by nuclear receptors. Mutations in this gene are associated with hepatocellular carcinomas. A pseudogene of this gene is found on chromosome1. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ARID2
• BP4: Computational evidence support a benign effect (MetaRNN=0.103184015).
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000212 (31/1461836) while in subpopulation AMR AF= 0.0000447 (2/44724). AF 95% confidence interval is 0.0000154. There are 0 homozygotes in gnomad4_exome. There are 14 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAdExome at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID2	NM_152641.4	c.2579A>G	p.Asn860Ser	missense_variant	15/21	ENST00000334344.11
ARID2	NM_001347839.2	c.2579A>G	p.Asn860Ser	missense_variant	15/20
ARID2	XM_047428489.1	c.2579A>G	p.Asn860Ser	missense_variant	15/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID2	ENST00000334344.11	c.2579A>G	p.Asn860Ser	missense_variant	15/21	1	NM_152641.4	P1
ARID2	ENST00000422737.7	c.2579A>G	p.Asn860Ser	missense_variant	15/20	1
ARID2	ENST00000444670.5	c.1427A>G	p.Asn476Ser	missense_variant	7/13	1
ARID2	ENST00000479608.5	c.*1129A>G		3_prime_UTR_variant, NMD_transcript_variant	9/15	1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251118 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135698

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461836 Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14 AN XY: 727218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	13
Dann	Benign	0.97
DEOGEN2	Benign	0.015	T;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T;.;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.28	N;N;N
REVEL	Benign	0.064
Sift	Benign	0.071	T;T;T
Sift4G	Benign	0.69	T;T;T
Polyphen		0.0020	B;.;B
Vest4		0.16
MutPred		0.41		Gain of catalytic residue at V862 (P = 0);.;.;
MVP		0.44
MPC		0.097
ClinPred		0.026	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.29

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: rs147193304; hg19: chr12-46244485; COSMIC: COSV57598412; COSMIC: COSV57598412;