2-56184719-C-G

Variant names:

• chr2-56184719-C-G
• rs1675922285
• NM_001080433.2:c.95C>G

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.95C>G​(p.Pro32Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,378,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P32L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CCDC85A NM_001080433.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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=0.19388756).

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.95C>G	p.Pro32Arg	missense	Exon 1 of 6	NP_001073902.1	Q96PX6
	CCDC85A	NM_001348512.1		c.95C>G	p.Pro32Arg	missense	Exon 1 of 7	NP_001335441.1
	CCDC85A	NM_001348513.1		c.95C>G	p.Pro32Arg	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.95C>G	p.Pro32Arg	missense	Exon 1 of 6	ENSP00000384040.2	Q96PX6
	ENSG00000233251	ENST00000432793.6	TSL:1	n.100+979G>C		intron	N/A
	CCDC85A	ENST00000894231.1		c.95C>G	p.Pro32Arg	missense	Exon 1 of 7	ENSP00000564290.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000218 AC: 3 AN: 1378730 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 680132

African (AFR) AF: 0.00 AC: 0 AN: 28452

American (AMR) AF: 0.00 AC: 0 AN: 34566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24542

East Asian (EAS) AF: 0.00 AC: 0 AN: 33696

South Asian (SAS) AF: 0.00 AC: 0 AN: 77410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4366

European-Non Finnish (NFE) AF: 0.00000279 AC: 3 AN: 1073874

Other (OTH) AF: 0.00 AC: 0 AN: 57244

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.26	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.1
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.061
Sift	Uncertain	0.018	D
Sift4G	Benign	0.13	T
Polyphen		0.49	P
Vest4		0.078
MutPred		0.48		Gain of helix (P = 0.0022)
MVP		0.20
MPC		0.091
ClinPred		0.40	T
GERP RS		1.5
Varity_R		0.047
gMVP		0.32
Mutation Taster		=81/19	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

dbSNP: rs1675922285; hg19: chr2-56411854;