2-27627123-C-T

Variant names:

• chr2-27627123-C-T
• rs142062417
• NM_024584.5:c.677G>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.677G>A​(p.Arg226Lys) 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 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. R226T) 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: 0.290
• 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=0.053600788).

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.677G>A	p.Arg226Lys	missense	Exon 2 of 2	NP_078860.2
	CCDC121	NM_001142683.3		c.1163G>A	p.Arg388Lys	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.677G>A	p.Arg226Lys	missense	Exon 2 of 2	ENSP00000339087.2	Q6ZUS5-1
	CCDC121	ENST00000394775.3	TSL:1	c.1163G>A	p.Arg388Lys	missense	Exon 2 of 2	ENSP00000412150.2	Q6ZUS5-2
	CCDC121	ENST00000866112.1		c.677G>A	p.Arg226Lys	missense	Exon 2 of 2	ENSP00000536171.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461800 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727196

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111938

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.0
DANN	Benign	0.55
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.29
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.053
Sift	Benign	0.54	T
Sift4G	Benign	0.56	T
Polyphen		0.0030	B
Vest4		0.049
MVP		0.23
MPC		0.20
ClinPred		0.023	T
GERP RS		2.5
Varity_R		0.039
gMVP		0.043
Mutation Taster		=99/1	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: rs142062417; hg19: chr2-27849990;