2-27626992-C-T

Variant names:

• chr2-27626992-C-T
• NM_024584.5:c.808G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024584.5(CCDC121):​c.808G>A​(p.Gly270Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 6.9e-7 (0 hom.)
• Consequence: CCDC121 NM_024584.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0810

Genes affected

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

ENSG00000259080 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047923833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC121	NM_024584.5	c.808G>A	p.Gly270Ser	missense_variant	Exon 2 of 2	ENST00000324364.4	NP_078860.2
CCDC121	NM_001142683.3	c.1294G>A	p.Gly432Ser	missense_variant	Exon 2 of 2		NP_001136155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC121	ENST00000324364.4	c.808G>A	p.Gly270Ser	missense_variant	Exon 2 of 2	1	NM_024584.5	ENSP00000339087.2
CCDC121	ENST00000394775.3	c.1294G>A	p.Gly432Ser	missense_variant	Exon 2 of 2	1		ENSP00000412150.2
ENSG00000259080	ENST00000505973.1	n.1389-2867C>T		intron_variant	Intron 12 of 17	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455704 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723712

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1294G>A (p.G432S) alteration is located in exon 2 (coding exon 2) of the CCDC121 gene. This alteration results from a G to A substitution at nucleotide position 1294, causing the glycine (G) at amino acid position 432 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.3
DANN	Benign	0.38
DEOGEN2	Benign	0.024	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.027
Sift	Benign	0.18	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.0020	B;.
Vest4		0.032
MutPred		0.11		Gain of glycosylation at G270 (P = 0.0205);.;
MVP		0.055
MPC		0.20
ClinPred		0.027	T
GERP RS		-0.86
Varity_R		0.057
gMVP		0.019

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27849859;