rs767303463

Variant names:

• chr2-196993654-C-A
• rs767303463
• NM_001195144.2:c.2852G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-196993654-C-A
• chr2-196993654-C-T

Variant summary

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

The NM_001195144.2(ANKRD44):​c.2852G>T​(p.Arg951Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000193 in 1,550,962 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R951C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKRD44 NM_001195144.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2852G>T	p.Arg951Leu	missense	Exon 27 of 28	NP_001182073.1	Q8N8A2-1
	ANKRD44	NM_001367495.1		c.2906G>T	p.Arg969Leu	missense	Exon 27 of 28	NP_001354424.1
	ANKRD44	NM_001367497.1		c.2852G>T	p.Arg951Leu	missense	Exon 27 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.2852G>T	p.Arg951Leu	missense	Exon 27 of 28	ENSP00000282272.9	Q8N8A2-1
	ANKRD44	ENST00000424317.5	TSL:1	c.2297G>T	p.Arg766Leu	missense	Exon 21 of 22	ENSP00000403415.1	H7C209
	ANKRD44	ENST00000647377.1		c.2852G>T	p.Arg951Leu	missense	Exon 27 of 28	ENSP00000496628.1	A0A2R8Y7Y4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000133 AC: 2 AN: 150908 AF XY: 0.0000124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000927

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398642 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689812

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.0000280 AC: 1 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35740

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079014

Other (OTH) AF: 0.00 AC: 0 AN: 58136

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74486

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000167 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.032	D
Vest4		0.51
MVP		0.87
ClinPred		0.90	D
GERP RS		5.0
Varity_R		0.49
gMVP		0.47

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: rs767303463; hg19: chr2-197858378;