chr9-70083123-G-C

Position:

• chr9-70083123-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153267.5(MAMDC2):​c.149-25088G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,062 control chromosomes in the GnomAD database, including 3,656 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (3656 hom., cov: 33)
• Consequence: MAMDC2 NM_153267.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889

Genes affected

MAMDC2 (HGNC:23673): (MAM domain containing 2) Predicted to enable glycosaminoglycan binding activity. Predicted to act upstream of or within peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

MAMDC2-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAMDC2	NM_153267.5	c.149-25088G>C		intron_variant		ENST00000377182.5	NP_694999.3
MAMDC2	NM_001347990.2	c.149-25088G>C		intron_variant			NP_001334919.1
MAMDC2	NR_125850.1	n.766-25088G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAMDC2	ENST00000377182.5	c.149-25088G>C		intron_variant		1	NM_153267.5	ENSP00000366387.4

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28052 AN: 151944 Hom.: 3635 Cov.: 33

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.185 AC: 28124 AN: 152062 Hom.: 3656 Cov.: 33 AF XY: 0.184 AC XY: 13676 AN XY: 74362

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.171

Alfa AF: 0.132 Hom.: 255

Bravo AF: 0.190

Asia WGS AF: 0.261 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.70
DANN	Benign	0.71

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: rs3015182; hg19: chr9-72698039;