12-45891802-G-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2 BP4_Strong BP6_Very_Strong BS1 BS2

The NM_152641.4(ARID2):c.4945G>C(p.Val1649Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000665 in 1,614,112 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (9 hom.)
• Consequence: ARID2 NM_152641.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 9.32

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 Benign. Variant got -19 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ARID2
• BP4: Computational evidence support a benign effect (MetaRNN=0.012111098).
• BP6: Variant 12-45891802-G-C is Benign according to our data. Variant chr12-45891802-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 133572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000473 (72/152264) while in subpopulation SAS AF= 0.00477 (23/4820). AF 95% confidence interval is 0.00326. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 72 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID2	NM_152641.4	c.4945G>C	p.Val1649Leu	missense_variant	17/21	ENST00000334344.11
ARID2	NM_001347839.2	c.4945G>C	p.Val1649Leu	missense_variant	17/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID2	ENST00000334344.11	c.4945G>C	p.Val1649Leu	missense_variant	17/21	1	NM_152641.4	P1

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00109 AC: 275 AN: 251254 Hom.: 4 AF XY: 0.00140 AC XY: 190 AN XY: 135774

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00470

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000828

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000685 AC: 1002 AN: 1461848 Hom.: 9 Cov.: 31 AF XY: 0.000865 AC XY: 629 AN XY: 727220

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.000651

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00499

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000404

Gnomad4 OTH exome AF: 0.000778

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.000604 AC XY: 45 AN XY: 74450

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000812 Hom.: 1

Bravo AF: 0.000400

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00134 AC: 163

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	ARID2: BS2 -

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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	0.020
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.039	T;T;.;.
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.012	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.97	N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.10	T;T;T;T
Sift4G	Uncertain	0.051	T;T;T;D
Polyphen		0.22	B;.;B;.
Vest4		0.74
MVP		0.72
MPC		0.18
ClinPred		0.054	T
GERP RS		5.2
Varity_R		0.32
gMVP		0.49

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: rs201268655; hg19: chr12-46285585; COSMIC: COSV57606957; COSMIC: COSV57606957;