2-130139636-C-A

Variant names:

• chr2-130139636-C-A
• NM_001258307.2:c.864G>T

Variant summary

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

The NM_001258307.2(CCDC74B):​c.864G>T​(p.Gln288His) 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: 34)
• Consequence: CCDC74B NM_001258307.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.409

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17277434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC74B	NM_001258307.2	c.864G>T	p.Gln288His	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.864G>T	p.Gln288His	missense_variant	Exon 8 of 8	1	NM_001258307.2	ENSP00000386294.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1062G>T (p.Q354H) alteration is located in exon 8 (coding exon 8) of the CCDC74B gene. This alteration results from a G to T substitution at nucleotide position 1062, causing the glutamine (Q) at amino acid position 354 to be replaced by a histidine (H). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	.;T
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.12
Sift	Benign	0.21	T;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.40	B;P
Vest4		0.27
MVP		0.67
MPC		0.45
ClinPred		0.88	D
GERP RS		2.8
Varity_R		0.30
gMVP		0.082

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: chr2-130897209;