chr2-241191225-C-G

Position:

• chr2-241191225-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370694.2(ANO7):​c.140C>G​(p.Ala47Gly) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANO7 NM_001370694.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.63

Genes affected

ANO7 (HGNC:31677): (anoctamin 7) This prostate-specific gene encodes a cytoplasmic protein, as well as a polytopic membrane protein which may serve as a target in prostate cancer diagnosis and immunotherapy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05480787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANO7	NM_001370694.2	c.140C>G	p.Ala47Gly	missense_variant	3/25	ENST00000674324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO7	ENST00000674324.2	c.140C>G	p.Ala47Gly	missense_variant	3/25		NM_001370694.2	A2
ANO7	ENST00000274979.12	c.302C>G	p.Ala101Gly	missense_variant	3/25	1		P2
ANO7	ENST00000402530.8	c.140C>G	p.Ala47Gly	missense_variant	3/4	1
ANO7	ENST00000402430.8	c.140C>G	p.Ala47Gly	missense_variant	3/22	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.302C>G (p.A101G) alteration is located in exon 3 (coding exon 3) of the ANO7 gene. This alteration results from a C to G substitution at nucleotide position 302, causing the alanine (A) at amino acid position 101 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	4.0
DANN	Benign	0.96
DEOGEN2	Benign	0.030	.;T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.31	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.038
Sift	Benign	0.069	T;T;T
Sift4G	Uncertain	0.048	D;T;T
Polyphen		0.46	P;B;.
Vest4		0.13
MutPred		0.18		Loss of stability (P = 0.0711);Loss of stability (P = 0.0711);Loss of stability (P = 0.0711);
MVP		0.15
MPC		0.11
ClinPred		0.094	T
GERP RS		0.73
Varity_R		0.026
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-242130640;