chr2-197000484-A-C

Position:

• chr2-197000484-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195144.2(ANKRD44):​c.2454T>G​(p.Asn818Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD44 NM_001195144.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.269

Genes affected

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

ANKRD44 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08194852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD44	NM_001195144.2	c.2454T>G	p.Asn818Lys	missense_variant	23/28	ENST00000282272.15	NP_001182073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD44	ENST00000282272.15	c.2454T>G	p.Asn818Lys	missense_variant	23/28	5	NM_001195144.2	ENSP00000282272.9
ANKRD44	ENST00000424317.5	c.1899T>G	p.Asn633Lys	missense_variant	17/22	1		ENSP00000403415.1
ANKRD44	ENST00000647377.1	c.2454T>G	p.Asn818Lys	missense_variant	23/28			ENSP00000496628.1
ANKRD44	ENST00000328737.6	c.2379T>G	p.Asn793Lys	missense_variant	23/26	2		ENSP00000331516.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2024

The c.2454T>G (p.N818K) alteration is located in exon 23 (coding exon 23) of the ANKRD44 gene. This alteration results from a T to G substitution at nucleotide position 2454, causing the asparagine (N) at amino acid position 818 to be replaced by a lysine (K). 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	Benign	0.34
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.025	.;.;T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.75	T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.082	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.70	.;.;N;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	N;.;.;N
REVEL	Benign	0.037
Sift	Benign	0.12	T;.;.;T
Sift4G	Benign	0.80	T;.;T;T
Vest4		0.26, 0.34
MVP		0.40
ClinPred		0.22	T
GERP RS		-3.3
Varity_R		0.099
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-197865208;