rs867595

chr9-70079625-T-G

Variant summary

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

The NM_153267.5(MAMDC2):c.149-28586T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,126 control chromosomes in the GnomAD database, including 3,982 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 0.19 (3982 hom., cov: 32)
• Consequence: MAMDC2 NM_153267.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAMDC2	NM_153267.5	c.149-28586T>G		intron_variant		ENST00000377182.5
MAMDC2	NM_001347990.2	c.149-28586T>G		intron_variant
MAMDC2	NR_125850.1	n.766-28586T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAMDC2	ENST00000377182.5	c.149-28586T>G		intron_variant		1	NM_153267.5	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28937 AN: 152008 Hom.: 3960 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.191 AC: 29010 AN: 152126 Hom.: 3982 Cov.: 32 AF XY: 0.190 AC XY: 14100 AN XY: 74376

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.176

Alfa AF: 0.125 Hom.: 826

Bravo AF: 0.197

Asia WGS AF: 0.262 AC: 911 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	14
Dann	Benign	0.78

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: rs867595; hg19: chr9-72694541;