Genetic Variant CCDC74A:p.Gly122Arg (chr2-131530647-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001349042.2(CCDC74A):c.490G>A(p.Gly164Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,612,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

CCDC74A
NM_001349042.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.27

Publications

7 publications found

Variant links:

Genes affected

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

CCDC74A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12434459).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349042.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC74A	NM_001258306.3	MANE Select	c.296-130G>A		intron	N/A	NP_001245235.1	Q96AQ1-2
CCDC74A	NM_001349042.2		c.490G>A	p.Gly164Arg	missense	Exon 3 of 8	NP_001335971.1
CCDC74A	NM_138770.4		c.364G>A	p.Gly122Arg	missense	Exon 3 of 8	NP_620125.1	Q96AQ1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC74A	ENST00000295171.10	TSL:1	c.364G>A	p.Gly122Arg	missense	Exon 3 of 8	ENSP00000295171.6	Q96AQ1-1
CCDC74A	ENST00000467992.6	TSL:1	c.364G>A	p.Gly122Arg	missense	Exon 3 of 7	ENSP00000444610.2	F5GZA4
CCDC74A	ENST00000409856.8	TSL:1 MANE Select	c.296-130G>A		intron	N/A	ENSP00000387009.3	Q96AQ1-2

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151694

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.0000329

AC:

AN:

243486

AF XY:

0.0000302

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000456

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000616

AC:

AN:

1460870

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

726710

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33468

American (AMR)

AF:

0.0000224

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52926

Middle Eastern (MID)

AF:

0.00630

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

1111710

Other (OTH)

AF:

0.000116

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151810

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41280

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67972

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.61

CADD

Benign

2.8

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0014

Eigen

Benign

-0.72

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.64

M_CAP

Benign

0.0093

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.3

PhyloP100

-1.3

PROVEAN

Benign

-0.010

REVEL

Benign

0.038

Sift

Pathogenic

0.0

Sift4G

Benign

0.80

Polyphen

1.0

Vest4

0.097

MutPred

0.41

Gain of sheet (P = 0.0085)

MVP

0.33

MPC

1.8

ClinPred

0.056

GERP RS

-2.8

Varity_R

0.089

gMVP

0.12

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over