Genetic Variant NM_152641.4:c.162C>G (chr12-45730113-C-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_152641.4(ARID2):c.162C>G(p.Val54Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ARID2
NM_152641.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.21

Publications

0 publications found

Variant links:

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]

ARID2 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Orphanet, ClinGen
Coffin-Siris syndrome 6
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ARID2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 12-45730113-C-G is Benign according to our data. Variant chr12-45730113-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2642909.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.21 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00000342 (5/1461334) while in subpopulation MID AF = 0.0007 (4/5712). AF 95% confidence interval is 0.000239. There are 0 homozygotes in GnomAdExome4. There are 4 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID2	NM_152641.4 link	c.162C>G	p.Val54Val	synonymous_variant	Exon 2 of 21	ENST00000334344.11	NP_689854.2
ARID2	NM_001347839.2 link	c.162C>G	p.Val54Val	synonymous_variant	Exon 2 of 20		NP_001334768.1	Q68CP9
ARID2	XM_047428489.1 link	c.162C>G	p.Val54Val	synonymous_variant	Exon 2 of 17		XP_047284445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID2	ENST00000334344.11 link	c.162C>G	p.Val54Val	synonymous_variant	Exon 2 of 21	1	NM_152641.4	ENSP00000335044.6		Q68CP9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461334

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726970

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000700

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111728

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ARID2: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

3.2

PromoterAI

0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over