chr6-31928196-C-G

Position:

• chr6-31928196-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282458.2(C2):​c.169+4C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,576,610 control chromosomes in the GnomAD database, including 25,370 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3300 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22070 hom.)
• Consequence: C2 NM_001282458.2 splice_region, intron
• Scores: Splicing: ADA: 0.00007353
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

Genes affected

C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]

ENSG00000244255 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2	NM_000063.6	c.256+32C>G		intron_variant		ENST00000299367.10	NP_000054.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2	ENST00000299367.10	c.256+32C>G		intron_variant		1	NM_000063.6	ENSP00000299367.5
ENSG00000244255	ENST00000456570.5	c.256+32C>G		intron_variant		2		ENSP00000410815.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30070 AN: 152044 Hom.: 3303 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.184 AC: 35810 AN: 194252 Hom.: 3848 AF XY: 0.193 AC XY: 20664 AN XY: 106822

Gnomad AFR exome AF: 0.286

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.167

Gnomad SAS exome AF: 0.325

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.166 AC: 236332 AN: 1424448 Hom.: 22070 Cov.: 29 AF XY: 0.170 AC XY: 120126 AN XY: 707328

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.198 AC: 30103 AN: 152162 Hom.: 3300 Cov.: 32 AF XY: 0.202 AC XY: 14998 AN XY: 74380

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.199

Alfa AF: 0.164 Hom.: 1366

Bravo AF: 0.191

Asia WGS AF: 0.338 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000074
dbscSNV1_RF	Benign	0.0060
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: rs7746553; hg19: chr6-31895973;