2-70979206-A-G

Variant names:

• chr2-70979206-A-G
• rs1669922591
• NM_001115116.2:c.280A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001115116.2(ANKRD53):​c.280A>G​(p.Lys94Glu) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K94N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD53 NM_001115116.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

ANKRD53 (HGNC:25691): (ankyrin repeat domain 53) Involved in mitotic metaphase plate congression; regulation of microtubule cytoskeleton organization; and regulation of mitotic cytokinesis. Located in spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258881 (HGNC:):

TEX261 (HGNC:30712): (testis expressed 261) Predicted to enable COPII receptor activity. Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Predicted to act upstream of or within positive regulation of apoptotic process. Predicted to be located in cytoplasm. Predicted to be integral component of membrane. Predicted to be active in COPII-coated ER to Golgi transport vesicle. Predicted to be integral component of Golgi membrane and integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040287524).
• BP6: Variant 2-70979206-A-G is Benign according to our data. Variant chr2-70979206-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3126892.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001115116.2. 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
	ANKRD53	NM_001115116.2	MANE Select	c.280A>G	p.Lys94Glu	missense	Exon 2 of 6	NP_001108588.1	Q8N9V6-1
	ANKRD53	NM_001369683.1		c.178A>G	p.Lys60Glu	missense	Exon 2 of 6	NP_001356612.1	C9JZ61
	ANKRD53	NM_024933.4		c.280A>G	p.Lys94Glu	missense	Exon 2 of 7	NP_079209.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD53	ENST00000360589.4	TSL:2 MANE Select	c.280A>G	p.Lys94Glu	missense	Exon 2 of 6	ENSP00000353796.3	Q8N9V6-1
	ANKRD53	ENST00000272421.10	TSL:1	c.280A>G	p.Lys94Glu	missense	Exon 2 of 7	ENSP00000272421.6	Q8N9V6-2
	ENSG00000258881	ENST00000606025.5	TSL:5	c.475+9709T>C		intron	N/A	ENSP00000475641.1	U3KQ87

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.7
DANN	Benign	0.47
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		1.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.095
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.34		Loss of ubiquitination at K94 (P = 0.0022)
MVP		0.38
MPC		0.51
ClinPred		0.052	T
GERP RS		1.9
Varity_R		0.064
gMVP		0.12
Mutation Taster		=99/1	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: rs1669922591; hg19: chr2-71206336;