rs778293897

Variant names:

• chr2-27627148-C-A
• NM_024584.5:c.652G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-27627148-C-A
• chr2-27627148-C-G
• chr2-27627148-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024584.5(CCDC121):​c.652G>T​(p.Ala218Ser) 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 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A218P) 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: 1.24

Genes affected

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

ENSG00000259080 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12558925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC121	NM_024584.5	c.652G>T	p.Ala218Ser	missense_variant	Exon 2 of 2	ENST00000324364.4	NP_078860.2
CCDC121	NM_001142683.3	c.1138G>T	p.Ala380Ser	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.652G>T	p.Ala218Ser	missense_variant	Exon 2 of 2	1	NM_024584.5	ENSP00000339087.2
CCDC121	ENST00000394775.3	c.1138G>T	p.Ala380Ser	missense_variant	Exon 2 of 2	1		ENSP00000412150.2
ENSG00000259080	ENST00000505973.1	n.1389-2711C>A		intron_variant	Intron 12 of 17	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461686 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727144

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.065
Sift	Benign	0.23	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;.
Vest4		0.051
MutPred		0.18		Loss of helix (P = 0.0376);.;
MVP		0.32
MPC		0.28
ClinPred		0.37	T
GERP RS		4.3
Varity_R		0.047
gMVP		0.013

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: chr2-27850015;