2-196998973-C-G

Variant names:

• chr2-196998973-C-G
• rs145698398
• NM_001195144.2:c.2599G>C

Variant summary

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

The NM_001195144.2(ANKRD44):​c.2599G>C​(p.Ala867Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,852 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A867T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: ANKRD44 NM_001195144.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 0 publications found

Genes affected

ANKRD44 (HGNC:25259): (ankyrin repeat domain 44)

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=0.25352916).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195144.2. 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
	ANKRD44	NM_001195144.2	MANE Select	c.2599G>C	p.Ala867Pro	missense	Exon 24 of 28	NP_001182073.1	Q8N8A2-1
	ANKRD44	NM_001367495.1		c.2653G>C	p.Ala885Pro	missense	Exon 24 of 28	NP_001354424.1
	ANKRD44	NM_001367497.1		c.2599G>C	p.Ala867Pro	missense	Exon 24 of 28	NP_001354426.1	A0A2R8Y7Y4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD44	ENST00000282272.15	TSL:5 MANE Select	c.2599G>C	p.Ala867Pro	missense	Exon 24 of 28	ENSP00000282272.9	Q8N8A2-1
	ANKRD44	ENST00000424317.5	TSL:1	c.2044G>C	p.Ala682Pro	missense	Exon 18 of 22	ENSP00000403415.1	H7C209
	ANKRD44	ENST00000647377.1		c.2599G>C	p.Ala867Pro	missense	Exon 24 of 28	ENSP00000496628.1	A0A2R8Y7Y4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.015
Eigen_PC	Benign	-0.066
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.9	M
PhyloP100		1.9
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.033	D
Vest4		0.51
MVP		0.70
ClinPred		0.80	D
GERP RS		5.0
Varity_R		0.12
gMVP		0.68
Mutation Taster		=63/37	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: rs145698398; hg19: chr2-197863697;