chr2-56184643-G-A

Variant names:

• chr2-56184643-G-A
• NM_001080433.2:c.19G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080433.2(CCDC85A):​c.19G>A​(p.Gly7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC85A NM_001080433.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• Publications: 0 publications found

Genes affected

CCDC85A (HGNC:29400): (coiled-coil domain containing 85A) Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000233251 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09253463).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080433.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC85A	NM_001080433.2	MANE Select	c.19G>A	p.Gly7Ser	missense	Exon 1 of 6	NP_001073902.1	Q96PX6
	CCDC85A	NM_001348512.1		c.19G>A	p.Gly7Ser	missense	Exon 1 of 7	NP_001335441.1
	CCDC85A	NM_001348513.1		c.19G>A	p.Gly7Ser	missense	Exon 1 of 6	NP_001335442.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC85A	ENST00000407595.3	TSL:1 MANE Select	c.19G>A	p.Gly7Ser	missense	Exon 1 of 6	ENSP00000384040.2	Q96PX6
	ENSG00000233251	ENST00000432793.6	TSL:1	n.100+1055C>T		intron	N/A
	CCDC85A	ENST00000894231.1		c.19G>A	p.Gly7Ser	missense	Exon 1 of 7	ENSP00000564290.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1285466 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 630694

African (AFR) AF: 0.00 AC: 0 AN: 24640

American (AMR) AF: 0.00 AC: 0 AN: 17738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18820

East Asian (EAS) AF: 0.00 AC: 0 AN: 30186

South Asian (SAS) AF: 0.00 AC: 0 AN: 62118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3660

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041008

Other (OTH) AF: 0.00 AC: 0 AN: 53230

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.052
Sift	Benign	0.23	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.29
MutPred		0.23		Gain of glycosylation at G7 (P = 0.0016)
MVP		0.17
MPC		0.085
ClinPred		0.16	T
GERP RS		2.7
Varity_R		0.065
gMVP		0.16
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr2-56411778;