chr10-97578579-G-C

Variant names:

• chr10-97578579-G-C
• rs981478720
• NM_001346793.2:c.430G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001346793.2(ANKRD2):​c.430G>C​(p.Gly144Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,408,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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 Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G144W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ANKRD2 NM_001346793.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.33
• Publications: 0 publications found

Genes affected

ANKRD2 (HGNC:495): (ankyrin repeat domain 2) This gene encodes a protein that belongs to the muscle ankyrin repeat protein (MARP) family. A similar gene in rodents is a component of a muscle stress response pathway and plays a role in the stretch-response associated with slow muscle function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346793.2. 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
	ANKRD2	NM_001346793.2	MANE Select	c.430G>C	p.Gly144Arg	missense	Exon 4 of 9	NP_001333722.1	A0A0A0MRN9
	ANKRD2	NM_001291218.2		c.769G>C	p.Gly257Arg	missense	Exon 4 of 9	NP_001278147.1
	ANKRD2	NM_020349.4		c.511G>C	p.Gly171Arg	missense	Exon 4 of 9	NP_065082.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD2	ENST00000370655.6	TSL:1 MANE Select	c.430G>C	p.Gly144Arg	missense	Exon 4 of 9	ENSP00000359689.1	A0A0A0MRN9
	ANKRD2	ENST00000307518.9	TSL:1	c.511G>C	p.Gly171Arg	missense	Exon 4 of 9	ENSP00000306163.5	Q9GZV1-1
	ANKRD2	ENST00000298808.9	TSL:1	c.511G>C	p.Gly171Arg	missense	Exon 4 of 8	ENSP00000298808.5	Q9GZV1-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408774 Hom.: 0 Cov.: 35 AF XY: 0.00000144 AC XY: 1 AN XY: 695758

African (AFR) AF: 0.00 AC: 0 AN: 32198

American (AMR) AF: 0.00 AC: 0 AN: 36648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25228

East Asian (EAS) AF: 0.00 AC: 0 AN: 36704

South Asian (SAS) AF: 0.00 AC: 0 AN: 79986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 9.22e-7 AC: 1 AN: 1084128

Other (OTH) AF: 0.00 AC: 0 AN: 58370

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.73		Gain of MoRF binding (P = 0.0694)
MVP		0.91
MPC		0.64
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.55
gMVP		0.75
Mutation Taster		=54/46	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: rs981478720; hg19: chr10-99338336;