rs1454301

Variant names:

• chr2-189945336-A-C
• rs1454301
• ENST00000478197.1:n.219+65509A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000478197.1(C2orf88):​n.219+65509A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,044 control chromosomes in the GnomAD database, including 6,435 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 0.26 (6435 hom., cov: 32)
• Consequence: C2orf88 ENST00000478197.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP19	XM_047446008.1	c.-518+47773A>C		intron_variant	Intron 2 of 6		XP_047301964.1
AKAP19	XM_047446009.1	c.-518+65658A>C		intron_variant	Intron 1 of 5		XP_047301965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2orf88	ENST00000478197.1	n.219+65509A>C		intron_variant	Intron 1 of 1	4
C2orf88	ENST00000495546.1	n.201+65509A>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40081 AN: 151926 Hom.: 6424 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.264 AC: 40145 AN: 152044 Hom.: 6435 Cov.: 32 AF XY: 0.259 AC XY: 19283 AN XY: 74348

African (AFR) AF: 0.460 AC: 19035 AN: 41424

American (AMR) AF: 0.210 AC: 3205 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1310 AN: 5178

South Asian (SAS) AF: 0.170 AC: 822 AN: 4824

European-Finnish (FIN) AF: 0.159 AC: 1680 AN: 10584

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12533 AN: 67980

Other (OTH) AF: 0.260 AC: 548 AN: 2108

Alfa AF: 0.208 Hom.: 1963

Bravo AF: 0.281

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.66
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs1454301; hg19: chr2-190810062;