6-31635993-A-G

Variant names:

• chr6-31635993-A-G
• rs11229
• NM_004638.4:c.5568A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The NM_004638.4(PRRC2A):​c.5568A>G​(p.Gln1856Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,611,550 control chromosomes in the GnomAD database, including 26,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.17 (2376 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24252 hom.)
• Consequence: PRRC2A NM_004638.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.240
• Publications: 35 publications found

Genes affected

PRRC2A (HGNC:13918): (proline rich coiled-coil 2A) A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. This gene has microsatellite repeats which are associated with the age-at-onset of insulin-dependent diabetes mellitus (IDDM) and possibly thought to be involved with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. This gene is also a candidate gene for the development of rheumatoid arthritis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.094).
• BP6: Variant 6-31635993-A-G is Benign according to our data. Variant chr6-31635993-A-G is described in ClinVar as [Benign]. Clinvar id is 3060509.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.5568A>G	p.Gln1856Gln	synonymous_variant	Exon 25 of 31	ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.5568A>G	p.Gln1856Gln	synonymous_variant	Exon 25 of 31		NP_542417.2
PRRC2A	XM_047419336.1	c.5568A>G	p.Gln1856Gln	synonymous_variant	Exon 25 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.5568A>G	p.Gln1856Gln	synonymous_variant	Exon 25 of 31	1	NM_004638.4	ENSP00000365201.2
PRRC2A	ENST00000376007.8	c.5568A>G	p.Gln1856Gln	synonymous_variant	Exon 25 of 31	1		ENSP00000365175.4
PRRC2A	ENST00000487089.1	n.634A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
PRRC2A	ENST00000487839.1	n.502A>G		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25658 AN: 151856 Hom.: 2376 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0788

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.145 AC: 36390 AN: 251022 AF XY: 0.145

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.0764

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.0961

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.176 AC: 256703 AN: 1459576 Hom.: 24252 Cov.: 35 AF XY: 0.174 AC XY: 126020 AN XY: 726238

African (AFR) AF: 0.206 AC: 6880 AN: 33422

American (AMR) AF: 0.0802 AC: 3586 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3103 AN: 26112

East Asian (EAS) AF: 0.0466 AC: 1851 AN: 39696

South Asian (SAS) AF: 0.115 AC: 9888 AN: 86188

European-Finnish (FIN) AF: 0.160 AC: 8551 AN: 53404

Middle Eastern (MID) AF: 0.0914 AC: 527 AN: 5766

European-Non Finnish (NFE) AF: 0.191 AC: 212393 AN: 1109994

Other (OTH) AF: 0.165 AC: 9924 AN: 60306

GnomAD4 genome AF: 0.169 AC: 25658 AN: 151974 Hom.: 2376 Cov.: 31 AF XY: 0.164 AC XY: 12202 AN XY: 74264

African (AFR) AF: 0.193 AC: 8010 AN: 41416

American (AMR) AF: 0.0983 AC: 1500 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3472

East Asian (EAS) AF: 0.0794 AC: 410 AN: 5166

South Asian (SAS) AF: 0.125 AC: 599 AN: 4808

European-Finnish (FIN) AF: 0.161 AC: 1709 AN: 10586

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.184 AC: 12513 AN: 67956

Other (OTH) AF: 0.148 AC: 311 AN: 2102

Alfa AF: 0.169 Hom.: 5886

Bravo AF: 0.166

Asia WGS AF: 0.0950 AC: 331 AN: 3478

EpiCase AF: 0.173

EpiControl AF: 0.165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PRRC2A-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.0
DANN	Benign	0.65
PhyloP100		0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11229; hg19: chr6-31603770; COSMIC: COSV52990781; COSMIC: COSV52990781;