chr2-97196724-T-A

Variant names:

• chr2-97196724-T-A
• rs534494159
• NM_001354587.1:c.2589T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 6P and 2B. PS1 PM2 BP4_Moderate

The NM_001354587.1(ANKRD36):​c.2589T>A​(p.Ser863Arg) 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. 15/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 48)
• Consequence: ANKRD36 NM_001354587.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 1 publications found

Genes affected

ANKRD36 (HGNC:24079): (ankyrin repeat domain 36)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PS1: Transcript NM_001354587.1 (ANKRD36) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12411907).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354587.1. 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
	ANKRD36	NM_001354587.1	MANE Select	c.2589T>A	p.Ser863Arg	missense	Exon 42 of 76	NP_001341516.1	A6QL64-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD36	ENST00000420699.9	TSL:5 MANE Select	c.2589T>A	p.Ser863Arg	missense	Exon 42 of 76	ENSP00000391950.4	A6QL64-1
	ANKRD36	ENST00000461153.7	TSL:5	c.2589T>A	p.Ser863Arg	missense	Exon 42 of 75	ENSP00000419530.3	A6QL64-1
	ANKRD36	ENST00000652721.1		c.2589T>A	p.Ser863Arg	missense	Exon 42 of 76	ENSP00000498611.1	A6QL64-1

Frequencies

GnomAD3 genomes Cov.: 48

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 48

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.14
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.46	T
Polyphen		0.94	P
Vest4		0.12
MutPred		0.16		Loss of phosphorylation at S863 (P = 0.0096)
MVP		0.47
ClinPred		0.22	T
GERP RS		0.67
Varity_R		0.078
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs534494159; hg19: chr2-97862461;