rs17006342

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_145207.3(AFG2A):c.807G>T(p.Leu269Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 1,614,158 control chromosomes in the GnomAD database, including 1,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 124 hom., cov: 33)

Exomes 𝑓: 0.040 ( 1410 hom. )

Consequence

AFG2A
NM_145207.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.111

Publications

4 publications found

Variant links:

Genes affected

AFG2A (HGNC:18119): (AFG2 AAA ATPase homolog A) This gene encodes a member of the ATPase associated with diverse activities family, whose members are defined by a highly conserved ATPase domain. Members of this family participate in diverse cellular processes that include membrane fusion, DNA replication, microtubule severing, and protein degradation. The protein encoded by this gene has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Allelic variants in this gene have been associated with epilepsy, hearing loss, and cognitive disability syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

AFG2A Gene-Disease associations (from GenCC):

microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, PanelApp Australia

AFG2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-122934398-G-T is Benign according to our data. Variant chr4-122934398-G-T is described in ClinVar as Benign. ClinVar VariationId is 475735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.111 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0306 (4657/152274) while in subpopulation NFE AF = 0.0417 (2837/68014). AF 95% confidence interval is 0.0404. There are 124 homozygotes in GnomAd4. There are 2452 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 124 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFG2A	NM_145207.3 link	c.807G>T	p.Leu269Leu	synonymous_variant	Exon 5 of 16	ENST00000274008.5	NP_660208.2	Q8NB90-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFG2A	ENST00000274008.5 link	c.807G>T	p.Leu269Leu	synonymous_variant	Exon 5 of 16	1	NM_145207.3	ENSP00000274008.3		Q8NB90-1

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4657

AN:

152156

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00642

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0389

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0417

Gnomad OTH

AF:

0.0210

GnomAD2 exomes

AF:

0.0341

AC:

8580

AN:

251370

AF XY:

0.0360

show subpopulations

Gnomad AFR exome

AF:

0.00659

Gnomad AMR exome

AF:

0.00795

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0895

Gnomad NFE exome

AF:

0.0400

Gnomad OTH exome

AF:

0.0344

GnomAD4 exome

AF:

0.0396

AC:

57822

AN:

1461884

Hom.:

1410

Cov.:

AF XY:

0.0399

AC XY:

29042

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00544

AC:

182

AN:

33480

American (AMR)

AF:

0.00823

AC:

368

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

409

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.0465

AC:

4012

AN:

86258

European-Finnish (FIN)

AF:

0.0865

AC:

4623

AN:

53418

Middle Eastern (MID)

AF:

0.0198

AC:

114

AN:

5768

European-Non Finnish (NFE)

AF:

0.0415

AC:

46185

AN:

1112006

Other (OTH)

AF:

0.0318

AC:

1923

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

3614

7228

10843

14457

18071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1708

3416

5124

6832

8540

<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:

0.0306

AC:

4657

AN:

152274

Hom.:

124

Cov.:

AF XY:

0.0329

AC XY:

2452

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00640

AC:

266

AN:

41558

American (AMR)

AF:

0.0130

AC:

199

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.0390

AC:

188

AN:

4824

European-Finnish (FIN)

AF:

0.101

AC:

1069

AN:

10596

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0417

AC:

2837

AN:

68014

Other (OTH)

AF:

0.0208

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

232

464

696

928

1160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0354

Hom.:

Bravo

AF:

0.0212

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0351

EpiControl

AF:

0.0346

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 14, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 01, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.41

(source)

DANN

Benign

0.58

PhyloP100

-0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over