2-197007898-A-G

Position:

• chr2-197007898-A-G

Variant summary

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

The NM_001195144.2(ANKRD44):​c.2038T>C​(p.Tyr680His) 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. 13/19 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)
• Consequence: ANKRD44 NM_001195144.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88

Genes affected

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

ANKRD44 (HGNC:):

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=0.28115487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD44	NM_001195144.2	c.2038T>C	p.Tyr680His	missense_variant	20/28	ENST00000282272.15	NP_001182073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD44	ENST00000282272.15	c.2038T>C	p.Tyr680His	missense_variant	20/28	5	NM_001195144.2	ENSP00000282272.9
ANKRD44	ENST00000424317.5	c.1483T>C	p.Tyr495His	missense_variant	14/22	1		ENSP00000403415.1
ANKRD44	ENST00000647377.1	c.2038T>C	p.Tyr680His	missense_variant	20/28			ENSP00000496628.1
ANKRD44	ENST00000328737.6	c.1963T>C	p.Tyr655His	missense_variant	20/26	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 07, 2022

The c.2038T>C (p.Y680H) alteration is located in exon 20 (coding exon 20) of the ANKRD44 gene. This alteration results from a T to C substitution at nucleotide position 2038, causing the tyrosine (Y) at amino acid position 680 to be replaced by a histidine (H). 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	0.31
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0083	.;.;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.85	T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.41	.;.;N;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	1.4	N;.;.;N
REVEL	Benign	0.18
Sift	Uncertain	0.023	D;.;.;T
Sift4G	Benign	0.31	T;.;T;T
Vest4		0.37, 0.40
MVP		0.56
ClinPred		0.49	T
GERP RS		5.2
Varity_R		0.096
gMVP		0.32

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: chr2-197872622;