rs199697684

Variant names:

• chr2-196989644-T-C
• rs199697684
• NM_001195144.2:c.2929A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001195144.2(ANKRD44):​c.2929A>G​(p.Arg977Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000158 in 1,550,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R977S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: ANKRD44 NM_001195144.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.88
• Publications: 0 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.02558291).

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.2929A>G	p.Arg977Gly	missense	Exon 28 of 28	NP_001182073.1	Q8N8A2-1
	ANKRD44	NM_001367495.1		c.*1036A>G		3_prime_UTR	Exon 28 of 28	NP_001354424.1
	ANKRD44	NM_001367497.1		c.*1036A>G		3_prime_UTR	Exon 28 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.2929A>G	p.Arg977Gly	missense	Exon 28 of 28	ENSP00000282272.9	Q8N8A2-1
	ANKRD44	ENST00000424317.5	TSL:1	c.2368+3939A>G		intron	N/A	ENSP00000403415.1	H7C209
	ANKRD44	ENST00000871701.1		c.2983A>G	p.Arg995Gly	missense	Exon 28 of 28	ENSP00000541760.1

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000201 AC: 30 AN: 149170 AF XY: 0.000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000488

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000727

Gnomad OTH exome AF: 0.000232

GnomAD4 exome AF: 0.000143 AC: 200 AN: 1397972 Hom.: 0 Cov.: 34 AF XY: 0.000184 AC XY: 127 AN XY: 689528

African (AFR) AF: 0.00 AC: 0 AN: 31588

American (AMR) AF: 0.000364 AC: 13 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35710

South Asian (SAS) AF: 0.000808 AC: 64 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48136

Middle Eastern (MID) AF: 0.000878 AC: 5 AN: 5698

European-Non Finnish (NFE) AF: 0.0000927 AC: 100 AN: 1078770

Other (OTH) AF: 0.000311 AC: 18 AN: 57966

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.000362 AC XY: 27 AN XY: 74494

African (AFR) AF: 0.0000481 AC: 2 AN: 41590

American (AMR) AF: 0.00144 AC: 22 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000261

ExAC AF: 0.000411 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.089
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Uncertain	0.020
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0061	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.9
PrimateAI	Uncertain	0.56	T
REVEL	Benign	0.25
Sift4G	Uncertain	0.037	D
Vest4		0.51
MVP		0.59
ClinPred		0.11	T
GERP RS		6.1
Varity_R		0.28
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs199697684; hg19: chr2-197854368;