2-130139569-G-T

Variant names:

• chr2-130139569-G-T
• NM_001258307.2:c.931C>A

Variant summary

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

The NM_001258307.2(CCDC74B):​c.931C>A​(p.Arg311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,052 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R311C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC74B NM_001258307.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.762

Genes affected

CCDC74B (HGNC:25267): (coiled-coil domain containing 74B)

MED15P9 (HGNC:):

MED15P9 (HGNC:44130): (mediator complex subunit 15 pseudogene 9)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC74B	NM_001258307.2	c.931C>A	p.Arg311Ser	missense_variant	Exon 8 of 8	ENST00000409943.8	NP_001245236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC74B	ENST00000409943.8	c.931C>A	p.Arg311Ser	missense_variant	Exon 8 of 8	1	NM_001258307.2	ENSP00000386294.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461052 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726824

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	.;T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.54
MVP		0.82
MPC		0.60
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.43
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: chr2-130897142;