2-97113864-A-T

Variant names:

• chr2-97113864-A-T
• rs550176856
• NM_001354587.1:c.125A>T

Variant summary

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

The NM_001354587.1(ANKRD36):​c.125A>T​(p.His42Leu) 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. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD36 NM_001354587.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

Genes affected

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

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=0.059060305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36	NM_001354587.1	c.125A>T	p.His42Leu	missense_variant	Exon 1 of 76	ENST00000420699.9	NP_001341516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD36	ENST00000420699.9	c.125A>T	p.His42Leu	missense_variant	Exon 1 of 76	5	NM_001354587.1	ENSP00000391950.4
ANKRD36	ENST00000452478.2	n.313A>T		non_coding_transcript_exon_variant	Exon 1 of 3	1
ANKRD36	ENST00000461153.7	c.125A>T	p.His42Leu	missense_variant	Exon 1 of 75	5		ENSP00000419530.3
ANKRD36	ENST00000652721.1	c.125A>T	p.His42Leu	missense_variant	Exon 1 of 76			ENSP00000498611.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.12
DANN	Benign	0.26
DEOGEN2	Benign	0.0011	.;.;.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.068	T;T;T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.059	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.33	.;.;.;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.51	.;N;.;N
REVEL	Benign	0.027
Sift	Benign	0.63	.;T;.;T
Sift4G	Benign	0.58	.;T;T;T
Polyphen		0.0	.;.;.;B
Vest4		0.14, 0.19, 0.12
MutPred		0.47		Loss of MoRF binding (P = 0.0793);Loss of MoRF binding (P = 0.0793);Loss of MoRF binding (P = 0.0793);Loss of MoRF binding (P = 0.0793);
MVP		0.35
ClinPred		0.035	T
GERP RS		-1.9
Varity_R		0.033

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

LitVar

Other links and lift over

dbSNP: rs550176856; hg19: chr2-97779601;