2-196993652-T-C

Variant names:

• chr2-196993652-T-C
• rs1300829029
• NM_001195144.2:c.2854A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001195144.2(ANKRD44):​c.2854A>G​(p.Asn952Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,398,678 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ANKRD44 NM_001195144.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35774544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD44	NM_001195144.2	c.2854A>G	p.Asn952Asp	missense_variant	Exon 27 of 28	ENST00000282272.15	NP_001182073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD44	ENST00000282272.15	c.2854A>G	p.Asn952Asp	missense_variant	Exon 27 of 28	5	NM_001195144.2	ENSP00000282272.9
ANKRD44	ENST00000424317.5	c.2299A>G	p.Asn767Asp	missense_variant	Exon 21 of 22	1		ENSP00000403415.1
ANKRD44	ENST00000647377.1	c.2854A>G	p.Asn952Asp	missense_variant	Exon 27 of 28			ENSP00000496628.1
ANKRD44	ENST00000486006.1	n.-14A>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000662 AC: 1 AN: 150994 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 80886

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398678 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689830

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2854A>G (p.N952D) alteration is located in exon 27 (coding exon 27) of the ANKRD44 gene. This alteration results from a A to G substitution at nucleotide position 2854, causing the asparagine (N) at amino acid position 952 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D;D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	.;.;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.8	D;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.015	D;.;.
Sift4G	Uncertain	0.044	D;.;D
Vest4		0.33
MVP		0.62
ClinPred		0.94	D
GERP RS		5.0
Varity_R		0.20
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs1300829029; hg19: chr2-197858376;