rs2975868

Variant names:

• chr9-70090691-G-C
• rs2975868
• NM_153267.5:c.149-17520G>C

Variant summary

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

The NM_153267.5(MAMDC2):​c.149-17520G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,006 control chromosomes in the GnomAD database, including 3,629 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 (3629 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MAMDC2 NM_153267.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAMDC2	NM_153267.5	c.149-17520G>C		intron_variant	Intron 2 of 13	ENST00000377182.5	NP_694999.3
MAMDC2	NM_001347990.2	c.149-17520G>C		intron_variant	Intron 2 of 11		NP_001334919.1
MAMDC2	NR_125850.1	n.766-17520G>C		intron_variant	Intron 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAMDC2	ENST00000377182.5	c.149-17520G>C		intron_variant	Intron 2 of 13	1	NM_153267.5	ENSP00000366387.4

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27966 AN: 151888 Hom.: 3609 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.163

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.184 AC: 28037 AN: 152006 Hom.: 3629 Cov.: 32 AF XY: 0.184 AC XY: 13643 AN XY: 74312

African (AFR) AF: 0.365 AC: 15113 AN: 41410

American (AMR) AF: 0.117 AC: 1790 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1063 AN: 5168

South Asian (SAS) AF: 0.229 AC: 1101 AN: 4812

European-Finnish (FIN) AF: 0.103 AC: 1092 AN: 10586

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.102 AC: 6962 AN: 67978

Other (OTH) AF: 0.169 AC: 356 AN: 2108

Alfa AF: 0.144 Hom.: 295

Bravo AF: 0.190

Asia WGS AF: 0.260 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.15
DANN	Benign	0.52
PhyloP100		-1.2
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: rs2975868; hg19: chr9-72705607;