rs10511979

Positions:

• chr9-70105522-G-A

Variant summary

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

The ENST00000377182.5(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 ENST00000377182.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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=-0.86).
• 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/exons	MANE	Protein	UniProt
MAMDC2	NM_153267.5	c.149-2689G>A		intron_variant		ENST00000377182.5	NP_694999.3
MAMDC2	NM_001347990.2	c.149-2689G>A		intron_variant			NP_001334919.1
MAMDC2	NR_125850.1	n.766-2689G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAMDC2	ENST00000377182.5	c.149-2689G>A		intron_variant		1	NM_153267.5	ENSP00000366387	P1
MAMDC2-AS1	ENST00000591368.5	n.778+394C>T		intron_variant, non_coding_transcript_variant		5
MAMDC2-AS1	ENST00000414515.7	n.106+8233C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.0693

Gnomad4 ASJ AF: 0.0960

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0979 Hom.: 410

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

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: rs10511979; hg19: chr9-72720438;