Genetic Variant CCDC87:p.Arg750His (chr11-66590767-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018219.3(CCDC87):c.2249G>A(p.Arg750His) variant causes a missense change. The variant allele was found at a frequency of 0.000939 in 1,612,722 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 1 hom. )

Consequence

CCDC87
NM_018219.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.34

Variant links:

Genes affected

CCDC87 (HGNC:25579): (coiled-coil domain containing 87) Predicted to be involved in positive regulation of acrosome reaction and positive regulation of fertilization. [provided by Alliance of Genome Resources, Apr 2022]

CCDC87 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC87	NM_018219.3 link	c.2249G>A	p.Arg750His	missense_variant	Exon 1 of 1	ENST00000333861.5	NP_060689.2	Q9NVE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC87	ENST00000333861.5 link	c.2249G>A	p.Arg750His	missense_variant	Exon 1 of 1	6	NM_018219.3	ENSP00000328487.3		Q9NVE4

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000728

AC:

182

AN:

249848

Hom.:

AF XY:

0.000747

AC XY:

101

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.000372

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.000978

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000973

AC:

1421

AN:

1460400

Hom.:

Cov.:

AF XY:

0.000928

AC XY:

674

AN XY:

726606

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000943

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000617

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000905

Hom.:

Bravo

AF:

0.000544

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000749

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2249G>A (p.R750H) alteration is located in exon 1 (coding exon 1) of the CCDC87 gene. This alteration results from a G to A substitution at nucleotide position 2249, causing the arginine (R) at amino acid position 750 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.71

M_CAP

Benign

0.077

MetaRNN

Uncertain

0.50

MetaSVM

Uncertain

0.17

MutationAssessor

Pathogenic

3.1

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.5

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.89

MVP

0.75

MPC

0.69

ClinPred

0.11

GERP RS

5.5

Varity_R

0.65

gMVP

0.67

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over