chr2-130139636-C-A

Variant names:

• chr2-130139636-C-A
• rs1284763648
• NM_001258307.2:c.864G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q288K) has been classified 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
• Publications: 0 publications found

Genes affected

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

MED15P9 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258307.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC74B	NM_001258307.2	MANE Select	c.864G>T	p.Gln288His	missense	Exon 8 of 8	NP_001245236.1	Q96LY2-2
	CCDC74B	NM_207310.4		c.1062G>T	p.Gln354His	missense	Exon 8 of 8	NP_997193.1	Q96LY2-1
	CCDC74B	NR_165309.1		n.1147G>T		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC74B	ENST00000409943.8	TSL:1 MANE Select	c.864G>T	p.Gln288His	missense	Exon 8 of 8	ENSP00000386294.3	Q96LY2-2
	CCDC74B	ENST00000860854.1		c.1074G>T	p.Gln358His	missense	Exon 8 of 8	ENSP00000530913.1
	CCDC74B	ENST00000944366.1		c.1074G>T	p.Gln358His	missense	Exon 8 of 8	ENSP00000614425.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.41
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.12
Sift	Benign	0.21	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.40	B
Vest4		0.27
MVP		0.67
MPC		0.45
ClinPred		0.88	D
GERP RS		2.8
Varity_R		0.30
gMVP		0.082
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1284763648; hg19: chr2-130897209;