rs11098682

Variant names:

• chr4-122947124-G-T
• rs11098682
• NM_145207.3:c.1459-109G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145207.3(AFG2A):​c.1459-109G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 1,082,886 control chromosomes in the GnomAD database, including 415,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (47056 hom., cov: 32)
  • Exomes 𝑓: 0.89 (368851 hom.)
• Consequence: AFG2A NM_145207.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0300
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-122947124-G-T is Benign according to our data. Variant chr4-122947124-G-T is described in ClinVar as Benign. ClinVar VariationId is 586674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFG2A	NM_145207.3	c.1459-109G>T		intron_variant	Intron 8 of 15	ENST00000274008.5	NP_660208.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFG2A	ENST00000274008.5	c.1459-109G>T		intron_variant	Intron 8 of 15	1	NM_145207.3	ENSP00000274008.3
AFG2A	ENST00000422835.2	n.1501-109G>T		intron_variant	Intron 8 of 14	1
AFG2A	ENST00000675612.1	c.1456-109G>T		intron_variant	Intron 8 of 16			ENSP00000502453.1
AFG2A	ENST00000674886.1	n.1521-109G>T		intron_variant	Intron 8 of 10

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115041 AN: 151976 Hom.: 47036 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.886 AC: 825037 AN: 930792 Hom.: 368851 AF XY: 0.888 AC XY: 408763 AN XY: 460484

African (AFR) AF: 0.393 AC: 8401 AN: 21364

American (AMR) AF: 0.804 AC: 13107 AN: 16304

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 13824 AN: 16158

East Asian (EAS) AF: 0.948 AC: 30342 AN: 31996

South Asian (SAS) AF: 0.896 AC: 41422 AN: 46248

European-Finnish (FIN) AF: 0.904 AC: 28254 AN: 31256

Middle Eastern (MID) AF: 0.799 AC: 2334 AN: 2920

European-Non Finnish (NFE) AF: 0.901 AC: 651778 AN: 723374

Other (OTH) AF: 0.864 AC: 35575 AN: 41172

GnomAD4 genome AF: 0.757 AC: 115110 AN: 152094 Hom.: 47056 Cov.: 32 AF XY: 0.761 AC XY: 56565 AN XY: 74372

African (AFR) AF: 0.415 AC: 17204 AN: 41430

American (AMR) AF: 0.796 AC: 12172 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2991 AN: 3470

East Asian (EAS) AF: 0.955 AC: 4957 AN: 5188

South Asian (SAS) AF: 0.894 AC: 4315 AN: 4824

European-Finnish (FIN) AF: 0.905 AC: 9556 AN: 10562

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61154 AN: 68012

Other (OTH) AF: 0.773 AC: 1635 AN: 2116

Alfa AF: 0.854 Hom.: 30865

Bravo AF: 0.732

Asia WGS AF: 0.901 AC: 3129 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 20, 2017

Athena Diagnostics

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	-0.87
CADD	Benign	2.1
DANN	Benign	0.33
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

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: rs11098682; hg19: chr4-123868279;