2-85754406-C-T

Variant names:

• chr2-85754406-C-T
• rs1396628855
• NM_032827.7:c.217C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032827.7(ATOH8):​c.217C>T​(p.Pro73Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. P73T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATOH8 NM_032827.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872
• Publications: 0 publications found

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]

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=0.08849424).

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.217C>T	p.Pro73Ser	missense	Exon 1 of 3	NP_116216.2	Q96SQ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATOH8	ENST00000306279.4	TSL:1 MANE Select	c.217C>T	p.Pro73Ser	missense	Exon 1 of 3	ENSP00000304676.3	Q96SQ7-1
	ATOH8	ENST00000716557.1		c.217C>T	p.Pro73Ser	missense	Exon 1 of 3	ENSP00000520563.1	Q96SQ7-1
	ATOH8	ENST00000881377.1		c.217C>T	p.Pro73Ser	missense	Exon 1 of 3	ENSP00000551436.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	5.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.87
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.77	N
REVEL	Benign	0.18
Sift	Benign	0.11	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.16
MutPred		0.28		Gain of glycosylation at P73 (P = 0.0056)
MVP		0.30
MPC		0.57
ClinPred		0.064	T
GERP RS		0.52
PromoterAI		0.069	Neutral
Varity_R		0.026
gMVP		0.11
Mutation Taster		=94/6	polymorphism

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: rs1396628855; hg19: chr2-85981529;