16-2527974-G-C

Position:

• chr16-2527974-G-C

Variant summary

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

The ENST00000293971.11(AMDHD2):​c.617G>C​(p.Cys206Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000551 in 1,452,906 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: 0.0000055 (0 hom.)
• Consequence: AMDHD2 ENST00000293971.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

Genes affected

AMDHD2 (HGNC:24262): (amidohydrolase domain containing 2) Enables N-acetylglucosamine-6-phosphate deacetylase activity. Predicted to be involved in N-acetylglucosamine catabolic process. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.28581774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMDHD2	NM_001330449.2	c.617G>C	p.Cys206Ser	missense_variant	5/11	ENST00000293971.11	NP_001317378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMDHD2	ENST00000293971.11	c.617G>C	p.Cys206Ser	missense_variant	5/11	1	NM_001330449.2	ENSP00000293971	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000551 AC: 8 AN: 1452906 Hom.: 0 Cov.: 33 AF XY: 0.00000553 AC XY: 4 AN XY: 722898

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000720

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

May 08, 2024

The c.617G>C (p.C206S) alteration is located in exon 5 (coding exon 5) of the AMDHD2 gene. This alteration results from a G to C substitution at nucleotide position 617, causing the cysteine (C) at amino acid position 206 to be replaced by a serine (S). 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	0.22
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Benign	0.83
DEOGEN2	Benign	0.17	T;.;.;.
Eigen	Benign	-0.011
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.79	T;T;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.1	L;L;L;.
MutationTaster	Benign	0.95	D;D;D;D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.42	N;N;N;.
REVEL	Uncertain	0.43
Sift	Benign	0.064	T;T;T;.
Sift4G	Uncertain	0.057	T;T;D;.
Polyphen		0.0040	B;B;B;.
Vest4		0.59
MutPred		0.40		Gain of disorder (P = 0.0153);Gain of disorder (P = 0.0153);Gain of disorder (P = 0.0153);Gain of disorder (P = 0.0153);
MVP		0.74
MPC		1.0
ClinPred		0.43	T
GERP RS		5.4
Varity_R		0.33
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr16-2577975;