9-38578015-T-C

Position:

• chr9-38578015-T-C

Variant summary

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

The NM_147195.4(ANKRD18A):​c.2381A>G​(p.Asp794Gly) 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. 13/21 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)
• Consequence: ANKRD18A NM_147195.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.478

Genes affected

ANKRD18A (HGNC:23643): (ankyrin repeat domain 18A)

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=0.14882714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD18A	NM_147195.4	c.2381A>G	p.Asp794Gly	missense_variant	13/16	ENST00000399703.6	NP_671728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD18A	ENST00000399703.6	c.2381A>G	p.Asp794Gly	missense_variant	13/16	1	NM_147195.4	ENSP00000382610	A2
ANKRD18A	ENST00000602295.5	c.551A>G	p.Asp184Gly	missense_variant	5/8	1		ENSP00000473463
ANKRD18A	ENST00000703205.1	c.2567A>G	p.Asp856Gly	missense_variant	15/18			ENSP00000515234	P2
ANKRD18A	ENST00000703204.1	c.*1341A>G		3_prime_UTR_variant, NMD_transcript_variant	10/17			ENSP00000515233

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

Apr 14, 2022

The c.2381A>G (p.D794G) alteration is located in exon 13 (coding exon 13) of the ANKRD18A gene. This alteration results from a A to G substitution at nucleotide position 2381, causing the aspartic acid (D) at amino acid position 794 to be replaced by a glycine (G). 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	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0063	.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	.;D
REVEL	Benign	0.036
Sift	Benign	0.22	.;T
Sift4G	Benign	0.063	T;D
Polyphen		0.99	.;D
Vest4		0.081
MutPred		0.18		.;Loss of stability (P = 0.0151);
MVP		0.13
MPC		0.22
ClinPred		0.41	T
GERP RS		0.25
Varity_R		0.12
gMVP		0.027

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr9-38578012;