Genetic Variant NM_032827.7:c.280G>A (chr2-85754469-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_032827.7(ATOH8):c.280G>A(p.Gly94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000533 in 1,312,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

ATOH8
NM_032827.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0730

Publications

0 publications found

Variant links:

Genes affected

ATOH8 (HGNC:24126): (atonal bHLH transcription factor 8) Enables DNA-binding transcription factor activity and E-box binding activity. Involved in several processes, including SMAD protein signal transduction; positive regulation of endothelial cell differentiation; and regulation of gene expression. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ATOH8 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07997924).

BP6

Variant 2-85754469-G-A is Benign according to our data. Variant chr2-85754469-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2468027.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032827.7. 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
	ATOH8	NM_032827.7	MANE Select	c.280G>A	p.Gly94Arg	missense	Exon 1 of 3	NP_116216.2	Q96SQ7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATOH8	ENST00000306279.4	TSL:1 MANE Select	c.280G>A	p.Gly94Arg	missense	Exon 1 of 3	ENSP00000304676.3	Q96SQ7-1
ATOH8	ENST00000716557.1		c.280G>A	p.Gly94Arg	missense	Exon 1 of 3	ENSP00000520563.1	Q96SQ7-1
ATOH8	ENST00000881377.1		c.280G>A	p.Gly94Arg	missense	Exon 1 of 3	ENSP00000551436.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000666

AC:

AN:

75124

AF XY:

0.0000233

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000466

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000533

AC:

AN:

1312264

Hom.:

Cov.:

AF XY:

0.00000466

AC XY:

AN XY:

643594

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25722

American (AMR)

AF:

0.000236

AC:

AN:

21150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18692

East Asian (EAS)

AF:

0.00

AC:

AN:

32442

South Asian (SAS)

AF:

0.00

AC:

AN:

65662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4302

European-Non Finnish (NFE)

AF:

0.00000190

AC:

AN:

1049904

Other (OTH)

AF:

0.00

AC:

AN:

53850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000282

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.31

CADD

Benign

7.0

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.073

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.50

MutationAssessor

Benign

0.46

PhyloP100

0.073

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.46

REVEL

Benign

0.15

Sift

Benign

0.24

Sift4G

Benign

0.27

Polyphen

0.086

Vest4

0.11

MutPred

0.20

Gain of methylation at G94 (P = 0.0216)

MVP

0.13

MPC

0.68

ClinPred

0.050

GERP RS

0.51

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.060

gMVP

0.15

Mutation Taster

=79/21

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over