dbSNP rs11894651: C2orf92:c.665+4C>A (chr2-97701308-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001351368.2(C2orf92):c.665+4C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 398,672 control chromosomes in the GnomAD database, including 95,255 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 0.68 ( 36398 hom., cov: 32)

Exomes 𝑓: 0.68 ( 58857 hom. )

Consequence

C2orf92
NM_001351368.2 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.00

Publications

11 publications found

Variant links:

Genes affected

C2orf92 (HGNC:49272): (chromosome 2 open reading frame 92) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C2orf92 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351368.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C2orf92	NM_001351368.2	MANE Select	c.665+4C>A	splice_region intron	N/A	NP_001338297.1	A0A1B0GVN3
C2orf92	NM_001410919.1		c.563+4C>A	splice_region intron	N/A	NP_001397848.1	A0A1B0GW88
C2orf92	NR_038386.2		n.1001+4C>A	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C2orf92	ENST00000627399.4	TSL:5 MANE Select	c.665+4C>A	splice_region intron	N/A	ENSP00000490587.1	A0A1B0GVN3
C2orf92	ENST00000451384.6	TSL:1	n.968+4C>A	splice_region intron	N/A
C2orf92	ENST00000599501.6	TSL:5	c.563+4C>A	splice_region intron	N/A	ENSP00000490827.1	A0A1B0GW88

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

103751

AN:

151954

Hom.:

36376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.702

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.621

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.773

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.734

Gnomad OTH

AF:

0.683

GnomAD4 exome

AF:

0.679

AC:

167556

AN:

246600

Hom.:

58857

Cov.:

AF XY:

0.679

AC XY:

84933

AN XY:

125000

show subpopulations

African (AFR)

AF:

0.708

AC:

5078

AN:

7176

American (AMR)

AF:

0.514

AC:

3820

AN:

7432

Ashkenazi Jewish (ASJ)

AF:

0.621

AC:

5740

AN:

9240

East Asian (EAS)

AF:

0.385

AC:

8820

AN:

22890

South Asian (SAS)

AF:

0.258

AC:

782

AN:

3030

European-Finnish (FIN)

AF:

0.774

AC:

16431

AN:

21220

Middle Eastern (MID)

AF:

0.594

AC:

769

AN:

1294

European-Non Finnish (NFE)

AF:

0.729

AC:

115197

AN:

157954

Other (OTH)

AF:

0.667

AC:

10919

AN:

16364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2448

4895

7343

9790

12238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

380

760

1140

1520

1900

<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

AF:

0.683

AC:

103821

AN:

152072

Hom.:

36398

Cov.:

AF XY:

0.675

AC XY:

50140

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.702

AC:

29105

AN:

41486

American (AMR)

AF:

0.576

AC:

8809

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.621

AC:

2154

AN:

3468

East Asian (EAS)

AF:

0.389

AC:

2007

AN:

5158

South Asian (SAS)

AF:

0.270

AC:

1298

AN:

4814

European-Finnish (FIN)

AF:

0.773

AC:

8172

AN:

10572

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.734

AC:

49901

AN:

67978

Other (OTH)

AF:

0.682

AC:

1437

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1615

3231

4846

6462

8077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.699

Hom.:

63261

Bravo

AF:

0.674

Asia WGS

AF:

0.396

AC:

1379

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

2.0

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over