chr2-197007889-T-C

Variant names:

• chr2-197007889-T-C
• NM_001195144.2:c.2047A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195144.2(ANKRD44):​c.2047A>G​(p.Ile683Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKRD44 NM_001195144.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.723
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063375115).

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.2047A>G	p.Ile683Val	missense	Exon 20 of 28	NP_001182073.1	Q8N8A2-1
	ANKRD44	NM_001367495.1		c.2101A>G	p.Ile701Val	missense	Exon 20 of 28	NP_001354424.1
	ANKRD44	NM_001367497.1		c.2047A>G	p.Ile683Val	missense	Exon 20 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.2047A>G	p.Ile683Val	missense	Exon 20 of 28	ENSP00000282272.9	Q8N8A2-1
	ANKRD44	ENST00000424317.5	TSL:1	c.1492A>G	p.Ile498Val	missense	Exon 14 of 22	ENSP00000403415.1	H7C209
	ANKRD44	ENST00000647377.1		c.2047A>G	p.Ile683Val	missense	Exon 20 of 28	ENSP00000496628.1	A0A2R8Y7Y4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461732 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727184

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111916

Other (OTH) AF: 0.00 AC: 0 AN: 60388

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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	0.099
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.60
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.035	N
PhyloP100		0.72
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.080
Sift	Benign	1.0	T
Sift4G	Benign	0.60	T
Vest4		0.12
MVP		0.25
ClinPred		0.055	T
GERP RS		4.1
Varity_R		0.054
gMVP		0.10
Mutation Taster		=92/8	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

hg19: chr2-197872613;