rs10511979

Variant names:

• chr9-70105522-G-A
• rs10511979
• NM_153267.5:c.149-2689G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153267.5(MAMDC2):​c.149-2689G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,186 control chromosomes in the GnomAD database, including 749 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 0.083 (749 hom., cov: 32)
• Consequence: MAMDC2 NM_153267.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 2 publications found

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:48719): (MAMDC2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAMDC2	NM_153267.5	c.149-2689G>A		intron_variant	Intron 2 of 13	ENST00000377182.5	NP_694999.3
MAMDC2	NM_001347990.2	c.149-2689G>A		intron_variant	Intron 2 of 11		NP_001334919.1
MAMDC2	NR_125850.1	n.766-2689G>A		intron_variant	Intron 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAMDC2	ENST00000377182.5	c.149-2689G>A		intron_variant	Intron 2 of 13	1	NM_153267.5	ENSP00000366387.4

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12558 AN: 152068 Hom.: 747 Cov.: 32

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.0826 AC: 12566 AN: 152186 Hom.: 749 Cov.: 32 AF XY: 0.0850 AC XY: 6326 AN XY: 74408

African (AFR) AF: 0.0201 AC: 834 AN: 41530

American (AMR) AF: 0.0693 AC: 1060 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0960 AC: 333 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1066 AN: 5170

South Asian (SAS) AF: 0.198 AC: 955 AN: 4822

European-Finnish (FIN) AF: 0.103 AC: 1093 AN: 10588

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6809 AN: 67996

Other (OTH) AF: 0.106 AC: 224 AN: 2114

Alfa AF: 0.0986 Hom.: 464

Bravo AF: 0.0742

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.79
PhyloP100		0.0080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10511979; hg19: chr9-72720438;