16-2530282-C-G

Position:

• chr16-2530282-C-G

Variant summary

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

The ENST00000293971.11(AMDHD2):​c.*719C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,010 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: 0.000013 (0 hom.)
• Consequence: AMDHD2 ENST00000293971.11 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.33

Genes affected

CEMP1 (HGNC:32553): (cementum protein 1) Enables hydroxyapatite binding activity. Involved in several processes, including biomineral tissue development; cell population proliferation; and odontogenesis. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07704702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEMP1	NM_001048212.3	c.*48G>C		3_prime_UTR_variant	1/1	ENST00000567119.1	NP_001041677.1
AMDHD2	NM_001330449.2	c.*719C>G		3_prime_UTR_variant	11/11	ENST00000293971.11	NP_001317378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMDHD2	ENST00000293971.11	c.*719C>G		3_prime_UTR_variant	11/11	1	NM_001330449.2	ENSP00000293971	P1
CEMP1	ENST00000567119.1	c.*48G>C		3_prime_UTR_variant	1/1		NM_001048212.3	ENSP00000457380	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461010 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 726746

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000479

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

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

Aug 23, 2021

The c.1308C>G (p.D436E) alteration is located in exon 11 (coding exon 11) of the AMDHD2 gene. This alteration results from a C to G substitution at nucleotide position 1308, causing the aspartic acid (D) at amino acid position 436 to be replaced by a glutamic acid (E). 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
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.15
DANN	Benign	0.78
DEOGEN2	Benign	0.0018	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.19	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.39	N;N
REVEL	Benign	0.12
Sift	Benign	0.067	T;D
Sift4G	Benign	0.10	T;D
Polyphen		0.0010	.;B
Vest4		0.11
MutPred		0.49		.;Gain of sheet (P = 0.0344);
MVP		0.048
MPC		0.0042
ClinPred		0.077	T
GERP RS		-4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
gMVP		0.068

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: rs2066069931; hg19: chr16-2580283;