2-196993637-C-T

Variant names:

• chr2-196993637-C-T
• rs2075960080
• NM_001195144.2:c.2869G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001195144.2(ANKRD44):​c.2869G>A​(p.Val957Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000572 in 1,398,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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. V957L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: ANKRD44 NM_001195144.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34445935).

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.2869G>A	p.Val957Ile	missense	Exon 27 of 28	NP_001182073.1	Q8N8A2-1
	ANKRD44	NM_001367495.1		c.2923G>A	p.Val975Ile	missense	Exon 27 of 28	NP_001354424.1
	ANKRD44	NM_001367497.1		c.2869G>A	p.Val957Ile	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.2869G>A	p.Val957Ile	missense	Exon 27 of 28	ENSP00000282272.9	Q8N8A2-1
	ANKRD44	ENST00000424317.5	TSL:1	c.2314G>A	p.Val772Ile	missense	Exon 21 of 22	ENSP00000403415.1	H7C209
	ANKRD44	ENST00000647377.1		c.2869G>A	p.Val957Ile	missense	Exon 27 of 28	ENSP00000496628.1	A0A2R8Y7Y4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000572 AC: 8 AN: 1398642 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 689822

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48350

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5704

European-Non Finnish (NFE) AF: 0.00000556 AC: 6 AN: 1079010

Other (OTH) AF: 0.0000172 AC: 1 AN: 58144

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	-0.040	N
PhyloP100		6.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.20
Sift	Uncertain	0.010	D
Sift4G	Benign	0.23	T
Vest4		0.35
MVP		0.60
ClinPred		0.83	D
GERP RS		5.2
Varity_R		0.059
gMVP		0.18

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: rs2075960080; hg19: chr2-197858361;