chr2-27627720-C-T

Variant names:

• chr2-27627720-C-T
• rs772625334
• NM_024584.5:c.80G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024584.5(CCDC121):​c.80G>A​(p.Arg27Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. R27P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC121 NM_024584.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 0 publications found

Genes affected

CCDC121 (HGNC:25833): (coiled-coil domain containing 121)

ENSG00000259080 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028679073).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024584.5. 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
	CCDC121	NM_024584.5	MANE Select	c.80G>A	p.Arg27Gln	missense	Exon 2 of 2	NP_078860.2
	CCDC121	NM_001142683.3		c.566G>A	p.Arg189Gln	missense	Exon 2 of 2	NP_001136155.1	Q6ZUS5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC121	ENST00000324364.4	TSL:1 MANE Select	c.80G>A	p.Arg27Gln	missense	Exon 2 of 2	ENSP00000339087.2	Q6ZUS5-1
	CCDC121	ENST00000394775.3	TSL:1	c.566G>A	p.Arg189Gln	missense	Exon 2 of 2	ENSP00000412150.2	Q6ZUS5-2
	CCDC121	ENST00000866112.1		c.80G>A	p.Arg27Gln	missense	Exon 2 of 2	ENSP00000536171.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250982 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461736 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727172

African (AFR) AF: 0.00 AC: 0 AN: 33478

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

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.061
DANN	Benign	0.66
DEOGEN2	Benign	0.015	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-2.2
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.89	N
REVEL	Benign	0.026
Sift	Benign	0.46	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.060
MutPred		0.14		Loss of MoRF binding (P = 0.1642)
MVP		0.15
MPC		0.25
ClinPred		0.043	T
GERP RS		-9.1
Varity_R		0.036
gMVP		0.023
Mutation Taster		=98/2	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: rs772625334; hg19: chr2-27850587; COSMIC: COSV99270517; COSMIC: COSV99270517;