chr11-86392604-A-G

Position:

• chr11-86392604-A-G

Variant summary

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

The NM_001156474.2(CCDC81):​c.362A>G​(p.Asp121Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000357 in 1,399,342 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: CCDC81 NM_001156474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.47

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC81	NM_001156474.2	c.362A>G	p.Asp121Gly	missense_variant	4/15	ENST00000445632.7	NP_001149946.1
CCDC81	NM_021827.5	c.286-2730A>G		intron_variant			NP_068599.3
LOC105369421	XR_007062826.1	n.81+3416T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC81	ENST00000445632.7	c.362A>G	p.Asp121Gly	missense_variant	4/15	1	NM_001156474.2	ENSP00000415528.2
CCDC81	ENST00000354755.5	c.286-2730A>G		intron_variant		2		ENSP00000346800.1
CCDC81	ENST00000531271.5	c.142-2730A>G		intron_variant		3		ENSP00000434959.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000357 AC: 5 AN: 1399342 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Oct 17, 2024

The c.362A>G (p.D121G) alteration is located in exon 4 (coding exon 4) of the CCDC81 gene. This alteration results from a A to G substitution at nucleotide position 362, causing the aspartic acid (D) at amino acid position 121 to be replaced by a glycine (G). 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	0.27
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.68		Loss of stability (P = 0.0306);
MVP		0.52
MPC		0.64
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.47
gMVP		0.72

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

Other links and lift over

dbSNP: rs982295758; hg19: chr11-86103646;