2-131527984-G-A

Variant names:

• chr2-131527984-G-A
• NM_001258306.3:c.14G>A

Variant summary

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

The NM_001258306.3(CCDC74A):​c.14G>A​(p.Gly5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC74A NM_001258306.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0420

Genes affected

CCDC74A (HGNC:25197): (coiled-coil domain containing 74A)

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=0.15200788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC74A	NM_001258306.3	c.14G>A	p.Gly5Glu	missense_variant	Exon 1 of 8	ENST00000409856.8	NP_001245235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC74A	ENST00000409856.8	c.14G>A	p.Gly5Glu	missense_variant	Exon 1 of 8	1	NM_001258306.3	ENSP00000387009.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000153 AC: 2 AN: 1305506 Hom.: 0 Cov.: 30 AF XY: 0.00000315 AC XY: 2 AN XY: 635192

Gnomad4 AFR exome AF: 0.0000353

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: 9.63e-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

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.14G>A (p.G5E) alteration is located in exon 1 (coding exon 1) of the CCDC74A gene. This alteration results from a G to A substitution at nucleotide position 14, causing the glycine (G) at amino acid position 5 to be replaced by a glutamic acid (E). 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	Uncertain	0.46
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0040	T;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.9	N;.;N
REVEL	Benign	0.021
Sift	Pathogenic	0.0	D;.;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.072
MutPred		0.34		Loss of MoRF binding (P = 0.0185);Loss of MoRF binding (P = 0.0185);Loss of MoRF binding (P = 0.0185);
MVP		0.19
MPC		2.4
ClinPred		0.41	T
GERP RS		0.84
Varity_R		0.092
gMVP		0.11

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: chr2-132285557;