2-130140237-C-T

Variant names:

• chr2-130140237-C-T
• rs368355157
• NM_001258307.2:c.620G>A

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.620G>A​(p.Arg207Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 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. R207M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCDC74B NM_001258307.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

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

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=0.10188186).

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.620G>A	p.Arg207Lys	missense	Exon 5 of 8	NP_001245236.1	Q96LY2-2
	CCDC74B	NM_207310.4		c.818G>A	p.Arg273Lys	missense	Exon 5 of 8	NP_997193.1	Q96LY2-1
	CCDC74B	NR_165309.1		n.903G>A		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC74B	ENST00000409943.8	TSL:1 MANE Select	c.620G>A	p.Arg207Lys	missense	Exon 5 of 8	ENSP00000386294.3	Q96LY2-2
	CCDC74B	ENST00000860854.1		c.830G>A	p.Arg277Lys	missense	Exon 5 of 8	ENSP00000530913.1
	CCDC74B	ENST00000944366.1		c.830G>A	p.Arg277Lys	missense	Exon 5 of 8	ENSP00000614425.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461344 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 726988

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111782

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.00073	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.052
Sift	Benign	0.18	T
Sift4G	Benign	0.085	T
Polyphen		0.0070	B
Vest4		0.088
MVP		0.41
MPC		1.4
ClinPred		0.10	T
GERP RS		2.3
Varity_R		0.045
gMVP		0.080
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs368355157; hg19: chr2-130897810;