11-86387574-G-A

Position:

• chr11-86387574-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001156474.2(CCDC81):​c.200G>A​(p.Gly67Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC81 NM_001156474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.61

Genes affected

CCDC81 (HGNC:26281): (coiled-coil domain containing 81) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

LOC105369421 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC81	NM_001156474.2	c.200G>A	p.Gly67Glu	missense_variant	3/15	ENST00000445632.7	NP_001149946.1
CCDC81	NM_021827.5	c.200G>A	p.Gly67Glu	missense_variant	3/14		NP_068599.3
LOC105369421	XR_007062825.1	n.210+193C>T		intron_variant
LOC105369421	XR_007062826.1	n.188+193C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC81	ENST00000445632.7	c.200G>A	p.Gly67Glu	missense_variant	3/15	1	NM_001156474.2	ENSP00000415528.2
CCDC81	ENST00000354755.5	c.200G>A	p.Gly67Glu	missense_variant	3/14	2		ENSP00000346800.1
CCDC81	ENST00000531271.5	c.141+1462G>A		intron_variant		3		ENSP00000434959.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

The c.200G>A (p.G67E) alteration is located in exon 3 (coding exon 3) of the CCDC81 gene. This alteration results from a G to A substitution at nucleotide position 200, causing the glycine (G) at amino acid position 67 to be replaced by a glutamic acid (E). 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	Uncertain	0.54
BayesDel_addAF	Benign	0.0025	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	.;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.64
MutPred		0.74		Gain of sheet (P = 0.0016);Gain of sheet (P = 0.0016);
MVP		0.71
MPC		0.70
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.86
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-86098616;