2-97158601-T-G

Variant names:

• chr2-97158601-T-G
• rs199723612
• NM_001354587.1:c.1335T>G

Variant summary

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

The NM_001354587.1(ANKRD36):​c.1335T>G​(p.Cys445Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. C445C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ANKRD36 NM_001354587.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475
• Publications: 0 publications found

Genes affected

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

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=0.14842662).

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.1335T>G	p.Cys445Trp	missense	Exon 17 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.1335T>G	p.Cys445Trp	missense	Exon 17 of 76	ENSP00000391950.4	A6QL64-1
	ANKRD36	ENST00000461153.7	TSL:5	c.1335T>G	p.Cys445Trp	missense	Exon 17 of 75	ENSP00000419530.3	A6QL64-1
	ANKRD36	ENST00000652721.1		c.1335T>G	p.Cys445Trp	missense	Exon 17 of 76	ENSP00000498611.1	A6QL64-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384268 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 683052

African (AFR) AF: 0.00 AC: 0 AN: 31584

American (AMR) AF: 0.00 AC: 0 AN: 35640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35524

South Asian (SAS) AF: 0.00 AC: 0 AN: 79154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078682

Other (OTH) AF: 0.0000173 AC: 1 AN: 57796

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.47
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.063
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.22
MutPred		0.40		Loss of disorder (P = 0.0542)
MVP		0.20
ClinPred		0.18	T
GERP RS		1.2
Varity_R		0.22
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs199723612; hg19: chr2-97824338;