rs1225684148

Variant names:

• chr2-56192624-G-T
• rs1225684148
• NM_001080433.2:c.424G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-56192624-G-T
• chr2-56192624-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080433.2(CCDC85A):​c.424G>T​(p.Ala142Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC85A NM_001080433.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33068007).

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>T	p.Ala142Ser	missense	Exon 2 of 6	NP_001073902.1	Q96PX6
	CCDC85A	NM_001348512.1		c.424G>T	p.Ala142Ser	missense	Exon 2 of 7	NP_001335441.1
	CCDC85A	NM_001348513.1		c.424G>T	p.Ala142Ser	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>T	p.Ala142Ser	missense	Exon 2 of 6	ENSP00000384040.2	Q96PX6
	CCDC85A	ENST00000894231.1		c.424G>T	p.Ala142Ser	missense	Exon 2 of 7	ENSP00000564290.1
	CCDC85A	ENST00000963878.1		c.424G>T	p.Ala142Ser	missense	Exon 2 of 6	ENSP00000633937.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249232 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461710 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60374

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	Benign	0.091
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0054	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L
PhyloP100		4.5
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.23
Sift	Benign	0.19	T
Sift4G	Benign	0.39	T
Polyphen		0.59	P
Vest4		0.55
MutPred		0.40		Gain of disorder (P = 0.0562)
MVP		0.23
MPC		0.38
ClinPred		0.45	T
GERP RS		5.3
Varity_R		0.084
gMVP		0.059
Mutation Taster		=91/9	polymorphism

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

dbSNP: rs1225684148; hg19: chr2-56419759; COSMIC: COSV68147208;