chr2-56192624-G-A

Variant names:

• chr2-56192624-G-A
• rs1225684148
• NM_001080433.2:c.424G>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.424G>A​(p.Ala142Thr) variant causes a missense change. 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. 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. A142S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC85A NM_001080433.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25173432).

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.424G>A	p.Ala142Thr	missense	Exon 2 of 6	NP_001073902.1	Q96PX6
	CCDC85A	NM_001348512.1		c.424G>A	p.Ala142Thr	missense	Exon 2 of 7	NP_001335441.1
	CCDC85A	NM_001348513.1		c.424G>A	p.Ala142Thr	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.424G>A	p.Ala142Thr	missense	Exon 2 of 6	ENSP00000384040.2	Q96PX6
	CCDC85A	ENST00000894231.1		c.424G>A	p.Ala142Thr	missense	Exon 2 of 7	ENSP00000564290.1
	CCDC85A	ENST00000963878.1		c.424G>A	p.Ala142Thr	missense	Exon 2 of 6	ENSP00000633937.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.16
Sift	Benign	0.22	T
Sift4G	Benign	0.27	T
Polyphen		0.59	P
Vest4		0.33
MutPred		0.53		Gain of phosphorylation at A142 (P = 0.0758)
MVP		0.24
MPC		0.23
ClinPred		0.73	D
GERP RS		5.3
Varity_R		0.11
gMVP		0.071
Mutation Taster		=78/22	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: rs1225684148; hg19: chr2-56419759; COSMIC: COSV68153608;