NM_001080433.2:c.287A>T

Variant names:

• chr2-56192487-A-T
• NM_001080433.2:c.287A>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001080433.2(CCDC85A):​c.287A>T​(p.Gln96Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CCDC85A NM_001080433.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95
• 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]

ENSG00000271894 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.869

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.287A>T	p.Gln96Leu	missense	Exon 2 of 6	NP_001073902.1	Q96PX6
	CCDC85A	NM_001348512.1		c.287A>T	p.Gln96Leu	missense	Exon 2 of 7	NP_001335441.1
	CCDC85A	NM_001348513.1		c.287A>T	p.Gln96Leu	missense	Exon 2 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.287A>T	p.Gln96Leu	missense	Exon 2 of 6	ENSP00000384040.2	Q96PX6
	CCDC85A	ENST00000894231.1		c.287A>T	p.Gln96Leu	missense	Exon 2 of 7	ENSP00000564290.1
	CCDC85A	ENST00000963878.1		c.287A>T	p.Gln96Leu	missense	Exon 2 of 6	ENSP00000633937.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1457882 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 724976

African (AFR) AF: 0.00 AC: 0 AN: 33312

American (AMR) AF: 0.00 AC: 0 AN: 44366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25692

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 85714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1109994

Other (OTH) AF: 0.00 AC: 0 AN: 60162

GnomAD4 genome Cov.: 32

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	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.015	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		8.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.58		Loss of ubiquitination at K97 (P = 0.0509)
MVP		0.58
MPC		0.46
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.80
gMVP		0.44
Mutation Taster		=39/61	disease causing

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

Other links and lift over

hg19: chr2-56419622;