rs6749643

Positions:

• chr2-189970747-G-A

Variant summary

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

The XM_047446008.1(C2orf88):​c.-518+73184G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,120 control chromosomes in the GnomAD database, including 5,135 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5135 hom., cov: 32)
• Consequence: C2orf88 XM_047446008.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

Genes affected

C2orf88 (HGNC:28191): (chromosome 2 open reading frame 88) Predicted to enable protein kinase A regulatory subunit binding activity. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2orf88	XM_047446008.1	c.-518+73184G>A		intron_variant			XP_047301964.1
C2orf88	XM_047446009.1	c.-518+91069G>A		intron_variant			XP_047301965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2orf88	ENST00000478197.1	n.219+90920G>A		intron_variant, non_coding_transcript_variant		4
C2orf88	ENST00000495546.1	n.201+90920G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36125 AN: 152002 Hom.: 5126 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.237

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.238 AC: 36171 AN: 152120 Hom.: 5135 Cov.: 32 AF XY: 0.233 AC XY: 17317 AN XY: 74390

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0995

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.239

Alfa AF: 0.190 Hom.: 6035

Bravo AF: 0.247

Asia WGS AF: 0.178 AC: 618 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6749643; hg19: chr2-190835473;